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Index

A Age-related dementia AAV1/2 serotype vector, 604 aging brain, 649 AAV4-BDNF/noggin, 603 application, 648 ABCA1, 783 cerebral exercise (mental training), 651 ACCORD (The Action to Control in cognitive function, 648 Cardiovascular Risk in Diabetes) factors, 648, 649 trial, 712 Hsp70, 649, 650 Acetyl-L-carnitine (ALCAR), 750 mental function, 651, 652 Acid-sensing ion channels (ASICs), 195 neuroprotection, aging brain, 652 Activated protein C (APC), 56, 69, 617, 619 oxidative stress, 649 Activating transcription factor 4 (ATF4), 589 pharmacological approaches, 650, 651 Active immunization, 554 physical exercise, 651, 652 Aβ, 555, 556 Age-Related Eye Disease Study (AREDS), 788 Activity-dependent neuroprotective protein Age-related macular degeneration (AMD), (ADNP), 56, 532 782, 783 Activity-dependent neurotrophic factor Aging brain (ADNF), 118, 532 age-related dementia, 649 Acute vs. chronic neuroprotection, 29 Aging, AD, 491 Adeno-associated virus vector (AAVgdnf), 438 cognitive impairment, 496, 497 Adeno-associated viruses (AAV), 603, 638 Creb protein, 553 Adenosine, 662, 664 GDF11 protein, 553, 554

Adenosine A2A receptor, 427 REST, 554 Adenosine A2A receptor (A2AR) AIDS antagonists, 741 dementia, 655, 656 Adenosine analogs AIMSPRO, 619

A1 receptors stimulation, 57 Air-circulating cooling blankets, 718 endogenous neuroprotective agent, 57 AL-108, 532 propentofylline, 58 Alcoholic neurologic disorders, 721 Adenosine monophosphate-activated protein Alcohol-induced damage, nervous system, 722 kinase (AMPK), 425–426 Aldehyde dehydrogenase 1 (ALDH1A1), 415 Adenosine receptor A2, 816 Alemtuzumab (Lemtrada), 690 Adhesion molecules, 184 Allosterically potentiating ligand (APL), 512 AdPEDF, 712 Aluminum, 492, 493 Advanced Combat Helmet (ACH), 322 Alzheimer Disease Assessment Scale- Aflibercept, 784 cognitive portion (ADAS-cog), 574

Alzheimer’s Disease Neuroimaging Initiative Anakinra, 619 (ADNI) cohort, 482 Anesthesia and surgery Alzheimer's disease (AD) anesthetic agents (see Anesthetic agents) aging, 553–554 cardiac surgery (see Cardiac surgery) anti-inflammatory drugs, 502–504 cardiovascular procedures antioxidant, 504–507 (see Cardiovascular procedures) antisense approaches, 507–508 monitoring of CNS function Aβ clearance, 512–515 (see Monitoring of CNS function) cell therapy, 508–512 neurosurgery (see Neurosurgery) cholesterol lowering agents, 515, 516 organ transplantation, 817 clinical trials, 560–575 perioperative cerebral damage, 809 gene therapy, 516–520 Anesthetic agents glutamate antagonists, 520, 521 barbiturates (see Barbiturates) inhibition of Aβ formation, 521–528 description, 196 management, 498, 499 etomidate, 804 MCI, 576–579 gaseous anesthetics (see Gaseous nanobiotechnology-based therapeutics, anesthetics) 530–531 ketamine, 805 neuroprotection, 575 lidocaine, 807 neuroprotective agents, 528–530 propofol, 196, 804, 805 neuroprotective approaches, 499 Angiogenin (ANG), 614 neuroprotective effect, 534–549 Angiotensin-converting enzyme (ACE) NTFs, 531–534 inhibitors nutritional approaches, 549–552 AD, 539 pathomechanism (see Pathomechanism) Angiotensin-II inhibitors PDE inhibitor, 552, 553 MS, 674, 675 phenserine, 501, 502 Angiotensin II receptor blockers therapeutic approaches, 560 (ARBs), 715 treatment, 498 Angiotensin receptor blockers (ARBs) vaccines, 554–558 AD, 540 vitamins, 558–560 Anoxic-ischemic neurological damage, 707 Amantadine, 299 Anthocyanin-loaded polyethylene glycol-gold Amino acid metabolism, 589 nanoparticles (PEG-AuNPs), 37 Aminoguanidine (AG), 232, 775 Antiangiogenic proteins, 793 AMPA/kainate receptors, 675 Anti-apoptosis agents AMX0035, 631 APC, 69 Amyloid cascade Calpain, primary protease, 70 secretases, 474, 475 caspase inhibitors, 70 Amyloid precursor protein (APP), 148 DNA binding drugs, 70 amyloid cascade hypothesis, 471 docosahexaenoic acid, 73 Aβ deposits and pathogenesis of AD, 473 lithium, 71 biological function, 471 melatonin, 71 intracellular domain, 471, 472 olesoxime, 72 mutations to CNS disorders, 472 omega-3 polyunsaturated fatty NEP, 474 acids, 72 nicastrin, 475 programmed cell death, 69 secretases, 474, 475 proNGF to sortilin binding, 74 Amyotrophic lateral sclerosis (ALS) Antiapoptotic agents clinical trials, 636 cyclophilin NIM811, 196 CRISPR/Cas9, 637, 638 lithium-induced neuroprotective multi-omics approach, 637 effects, 197 neuroprotective therapies NMDA receptors, 196 (see Neuroprotective therapies) oral creatine administration, 197 pathomechanisms, 638 phenserine, 501, 502 pathophysiology (see Pathophysiology) TUDCA, 198 Index 831

Antiapoptotic strategies, 427, 428 Antioxidant Anti-Aβ humoral immune response, 556 AD Anticholinesterase therapeutics, 507 colostrinin, 504, 505 Antidepressants curcumin, 505 ECS therapy, 59 DHA, 505, 506 fluoxetine, 60 melatonin, 506 induced neurogenesis, 58 resveratrol, 506, 507 neurodegenerative disorders, 58 agents, 748 Antidiabetic drugs MS, 675 AD Antioxidant approach clinical trials, 537 carnosine (β-alanyl-L-histidine), 201 insulin, 538 cell signaling-mediated damage, 201 metformin, 538 dehydroascorbic acid (DHA), 202 rosiglitazone, 538, 539 free radicals, 201 streptozotocin-induced oxidative damage, 201 neurodegeneration, 537 tocotrienols, 203 Antiepileptic drugs (AEDs) uric acid (UA), 203 AD Antioxidants/free radical scavengers lamotrigine, 535 free radical generation, 75 LEV, 535 natural defenses against oxidative epilepsy, 658, 660 stress, 75 Tiagabine, 199 Antipsychotic D2 and 5-HT1A Topiramate, 199 antagonists, 591 Antigen presenting cells (APC), 674 Antipsychotics, 594 Antiglutamate agents, 776 Antisense MS, 675 to AD Anti-HMGB1 monoclonal antibody, 200 anticholinesterase therapeutics, 507 Antihypertensive drugs APP, 507 AD lower Aβ, 507 ACE inhibitors, 539 PNAs, 508 ARBs, 540 preproenkephalin, 507 Antiinflammatory agents tau, 508 COX-2 inhibitors, 200 MS, 675, 676 minocycline, 201 Antisense oligonucleotides (ASOs), 508, Antiinflammatory drugs 604, 620 AD Antisense PNAs etanercept, 502, 503 in AD, 508 NSAIDS, 503, 504 Antisense tau PPARgamma, 504 AD, 508 Antimicrobial drugs Antiviral therapy AD in AD, 536, 537 antiviral therapy, 536, 537 Aortic aneurysms, 815, 816 vs. Cpn, 536 Apixaban, novel factor Xa inhibitor, 206 dapsone, 535, 536 APOE gene, 294 Anti-neuroinflammatory agents ApoE-containing lipoproteins, 515 aspirin (acetylsalicylic acid), 63 Apoptosis, 407, 589 gold microparticles, 66 Apoptosis model, 32, 33 interleukin-1 (IL-1), 64 APP intracellular domain (AICD), 471, 472 minocycline, 66 APP with the Swedish mutation (APPSw), 524 MMP expression, 66 Appel ALS rating scale (AALS), 626 nimesulide, 65 Approved antiepileptic drugs (AEDs) Anti-NMDA receptor (NMDAR) BIS-001 (Supernus Pharmaceuticals), 61 encephalitis, 698 Levetiracetam, 62 Anti-N-terminal huntingtin intrabodies Phenytoin, 62 (C4 sFv), 599 VPA, 63 832 Index

Arimoclomol, 204, 620, 621 B Arteriovenous malformations (AVMs), 190, BACE1 inhibitor, 524–526 234, 818 Bacterial meningitis Aspirin, 654 neural injury, 703, 704 Astrocytes, 5, 6, 510 neuroprotection strategies, 704 Astrocytic glycogen-derived lactate, 4 Barbiturates, 299 Asymptomatic carotid stenosis, 247 disadvantages, 803, 804 ATL1102 (Antisense Therapeutics/ISIS), hypoxia and ischemia, 803 675, 676 mechanisms, 803 Atorvastatin, 750 temperature, 803 ATP13A2, 428 thiopental, 804 Autism spectrum disorders (ASD) Bax, 599 synaptopathies, 647 BBB Autologous adipose tissue derived MSCs MS, 694 AD, 510 with imatinib, 673 Autologous bone marrow stem BBB damage, 289 cell therapy B-cell depletion therapy (BCDT), 676 MS, 677 Bcl-2, 599 Autologous hematopoietic stem BDNF and noggin, expression, 603 cells, 632 Betaxolol, 776, 779 Autologous non-myeloablative HSC Bevacizumab, 785 transplantation, 678 Bevasiranib, 795 Autologous stem cells Bexarotene dementia, 511, 512 AD, 540 Axon injury, 20 Bilirubin encephalopathy, 713, 714 Axona BioFocus, 633 AD, 549, 550 Biological approaches Axonal damage, 287, 288 TBI Aβ clearance antisense treatment, 316 AD cell therapy (see Cell therapy) galantamine-induced, 512 gap junctions, 316 monoclonal antibodies, 512–514 gene therapy, 319 nanotechnology, 514, 515 vaccines, 319 Nilotinib, 515 Biological therapies Aβ degradation cell, 248 NEP, 474 gene, 249 Aβ deposits immortalized cell grafts, 249 and AD pathogenesis, 473 instrinsic stem cells, 249 dsDNA breaks, 478, 479 stem cells (SCs) transplant, 248 neuron-specific Na+/K+-ATPaseα 3 Biomarkers, 21 subunit, 477 Bispectral index (BIS), 807 neurotoxicity, 479, 480 BK virus, 705 plaque-enriched regions, 476 Blast injury sequelae, 286 production and clearance, Blast TBI (bTBI), 284 476, 477 Blood-brain barrier (BBB), 8 synaptic activity, 478 Bone marrow (BM) cells, 357 synaptic and cognitive deficits, 477 Bone marrow-derived microglia, 508, 509 Aβ formation Bone morphogenetic proteins (BMPs), 118, 509 AD Bradykinin (BK), 300 chelation, 522–523 Brain derived neurotrophic factor (BDNF) secretase modulators, 524–528 AD, 532, 533 Aβ42, 469 mRNA levels, 521 Aβ-derived diffusible ligands (ADDL), 483 NSCs, 511 Index 833

Brain ECS volume pharmacological strategies, 816 HA preservation, 664 remacemide, 812 Brain imaging, 34 Cardiopulmonary bypass, 811 Brain metabolism Cardiovascular disorders AD, 480, 481 hypertension, 709 Brain myelin, 672 hypertensive encephalopathy, 708, 709 Brain tissue, gene expression, 5 myocardial infarction, 707, 708 Brain tumors, 823, 824 Cardiovascular procedures Brain-derived neurotrophic factor (BDNF), CNS complications, cardiac surgery, 810 119, 219, 375, 595, 781 Carotid endarterectomy, 822, 823 Brain-penetrating ACE inhibitors, 539 Caspase inhibitors, 70, 591 Brain-wide paravascular pathway, 476 Cav1.3 Ca2+ channels, 413 Branched chain amino acids (BCAAs), 310 Ceftriaxone, 621, 655 Brimonidine (BMD), 770, 779 Cell therapies, 430 Buckminsterfullerene C60 derivatives, 38 PD CNO, 432 DA neurons, 431 C D3 receptor, 430 C1-esterase inhibitor (C1-INH), 213 endogenous stem cells, 430 Cadmium telluride (CdTe) nanoparticles, 38, 39 hPSC, 432 Calcium channel blockers, 110 NPCs, 430 Calcium overload, 180 NSCs, 431 California Project to Cure Blindness–RPE1 NtCell, 431 (CPCB-RPE1), 793 pluripotent stem cell-derived neurons, Calorie restriction (CR), 159, 425 432 Cannabidiol (CBD), 104 transplantation of iPSC-derived neural Cannabinoids, 529 progenitors, 433 MS, 680, 681 SCI Carbon monoxide (CO), 84 fetal neural grafts, 353 loss of consciousness, 730 glial cells transplantation, 356 management, 732 OECs, 353, 354 mild acute, 730 OPCs, 355 neurologic and psychiatric Schwann cells transplantation, 356 manifestations, 730 stem cell (see Stem cells) pathomechanism, 731, 732 TBI Carbon monoxide-hypoxia, 731 clinical trial, 317 Cardiac arrest, 732, 733, 813 effects, 316 Cardiac glycosides, 204 HSCs, 317 Cardiac surgery limitations, 317, 318 anticipated/induced cardiac arrest, 813 MSC-derived exosomes, 318 aortic aneurysms, 815, 816 transplantation, 317 CABG Cell therapy anesthesia, 814 AD dexanabinol, 814 bone marrow-derived microglia, gaseous microembolization, 815 508, 509 postoperative neurocognitive cell transplantation, 602 injury, 814 CD11b promoter, 508 cardiopulmonary bypass, 813 CPECs, 509 drugs, 811 stem cell-based therapy, 603, 604 efficacy, erythropoietin, 813 stem cell transplantation, 509–512 HBO preconditioning (PC), 815 adenosine, 661 lidocaine, 812 diabetic neuropathy, 754 neuroprotection, 811 hESC-derived RPE cells, AMD, 792, 793 834 Index

Cell therapy (cont.) Cerebrospinal fluid (CSF) circulatory MS disorders autologous bone marrow stem cell aging CNS, 701 therapy, 677 brain catabolites, 701 cannabinoids, 680, 681 hydrocephalus, 701, 702 dysmyelinated mutant mouse NPH, 702 model, 676 Cerebrovascular disease ESCs, 677 classification, 178 HSCT, 678 stroke (see Stroke) MGE cell grafting, 679 Cerebrovascular malformations MSCs, 679, 680 AVMs, 190, 234 NaVI.5, 677, 678 CCMs, 191, 235, 236 NPCs, 680 Ceria nanoparticles, 39 NSC transplantation, 679 Cerliponase alfa, 386, 387 olfactory ensheathing cells, 677 Ceroid lipofuscinosis type 2 (CLN2), 385 T cell-based personalized vaccine, 680 Charcot-Marie-Tooth disease 1A (CMT1A), 757 transplantation strategies, 676 Chelation neural progenitor cells, 792 AD pharmacoresistant epilepsies, 662 clioquinol, 522 post-traumatic epilepsy (PTE), 661 copper, 522, 523 RPE, 790, 791 next generation multifunctional stem cell transplantation, 791, 792 agents, 523 TLE, 661, 662 Chemotherapy-induced brain damage, Central retinal artery occlusion (CRAO), 781 720, 721 Ceramide Chemotherapy-induced neuropathy AD, 544 PNS, 755, 756 Cerebral atrophy, 469 Chitosan nanoparticles, 40 Cerebral cavernous malformations (CCMs), Chlamydia pneumoniae (Cpn) 191, 235, 236 vs. antimicrobial drugs, 536 Cerebral dopamine neurotrophic factor Cholestatic liver diseases, 595 (CDNF), 220, 447 Cholesterol lowering agents Cerebral edema, 182, 287 AD, 515, 516 Cerebral exercise (mental training) Choline supplementation age-related dementia, 651 AD, 550 Cerebral hypoperfusion, 811 Cholinergic-mediated seizures Cerebral hypoxia miR-211, 665, 666 adaptive mechanisms, 24, 25 Chondroitin sulfate proteoglycans cerebral metabolism, 23, 24 (CSPGs), 343 description, 22 Chondroitinase ABC (ChABC), 343 effect on brain, 23 Choroid plexus epithelial cells (CPECs) HIFs and Hsps, 22 AD, 509 Cerebral hypoxia/ischemia, 283, 284 Choroidal neovascularization (CNV), 795 Cerebral infarction Chronic adult hydrocephalus, 702 penumbra, 188, 189 Chronic inflammatory demyelinating stress response and glial activation, 187 polyradiculoneuropathy zones of, 187 (CIDP), 756 Cerebral ischemia Chronic intermittent hypoxia (CIH), 735 pathophysiology (see Pathophysiology) Chronic myeloid leukemia (CML), 442 reperfusion injury, 187 Chronic traumatic encephalopathy (CTE), 289 Cerebral malaria (CM) brain tau deposition, 290 CNS infections, 707 clinical features, 290 Cerebral metabolism, 7 neurodegenerative disease, 290 Cerebral perfusion pressure (CPP), 296 neurofibrillary degeneration, 290 Cerebrolysin, 528 neuropathological findings, 291 Index 835

pathological findings, 291 Cogane™, 433 symptoms, 290 Cognitive deficits TDP-43, 291 AD, 484 Chronic unpredictable stress (CUS), 741 Cognitive reserve (CR), 160 Ciliary neurotrophic factor (CNTF), 119, 786 Colivelin, 125 Circadian rhythms, 8 Colostrinin, 504, 505 c-Jun N-terminal kinase (JNK), 589 Combinatorial therapies, 602 Cladribine Comorbidities, 539 MS, 681, 682 Conserved dopamine neurotrophic factor Classification, neuroprotective agents (CDNF), 434 ADNP, 56 Continuation ECT (C-ECT), 739 APC, 56 Copper, 493, 494 Davunetide, 57 chelation, 522, 523 dexmedetomidine, 56 Coronary artery bypass grafting (CABG), Clenbuterol, 204 813, 814 Clinical Dementia Rating (CDR) scale, 529 Corticotropin-releasing hormone (CRH), 146 Clinical trials COX-2 inhibitors, 200, 301, 302 AD, 560–575 Cranioplasty, 825 ALS, 636 Creatine, 311 MS, 671 neuroprotective effect, 311 optic nerve, 796 parameters, 311 PD, 455 pre-emptive, 311 retina, 796 Creatine supplementation, 311 SCI, 363 CREB-regulated transcription coactivator 1 TBI (TORC1), 599 completed or ongoing (only one), 328 Crenezumab, 512, 513 failed, 330, 331 (see Failed clinical Creutzfeldt-Jakob disease trails) 2-aminothiazoles, 395, 396 Clinically isolated syndrome (CIS), 695 extraneural infection, 394 Clioquinol flupirtine, 395 AD, 522 nontranscriptional mechanism, 395 Clozapine-N-oxide (CNO), 432 pharmacological approaches, 394 Clustered regularly interspaced short PrP gene, 394 palindromic repeats associated PrPSc conformation, 394 (CRISPR), 794 quinacrine, 394 Clustered regularly interspaced short symptoms, 393 palindromic repeats associated Cas9 Creutzfeldt-Jakob disease (CJD), 393 (CRISPR-Cas9), 606, 624, 637, 638 Cryptococcal meningitis CNS disorders, 472 CNS infections, 705 CNS glucocerebrosidase activity, 428, 429 CSP-1103, 544 CNS infections Curcumin, 206, 505 bacterial meningitis, 703–704 MS, 682 CM, 707 CXCL-12, 679 cryptococcal meningitis, 705 Cyclic AMP response element binding (Creb) PML, 704, 705 protein rabies virus, 706 AD, 553 Coagulation inhibitors Cyclic nucleotides, 596 Apixaban, novel factor Xa inhibitor, 206 Cyclin-dependent kinase (CDK) inhibitors, 301 heparin and enoxaparin, 205 Cyclin-dependent kinase 5 (Cdk5), 372 warfarin vs. dabigatran, 205, 206 Cyclooxygenase (COX)-2 inhibitors, 65 Cocktail of dietary supplements Cyclooxygenase-2 (COX-2), 621, 622 AD, 550 Cyclophilin inhibitors Coenzyme Q10 (CoQ10), 621 MS, 682 Coffee, 655 Cyclosporine, 302, 817 836 Index

Cysteamine, 593 FTD, 383, 384 Cysteine and neuroprotection LBD, 655 cysteamine, 593 Lewy bodies, 383 cysteine metabolism reprogramming, 593 PSP, 384 Cysteine stress, 589 and stress-induced neuropsychiatric Cysteine-string protein-α (CSPα), 372 disorders, 742 Cytokine-directed therapies vascular, 652–654 MS, 682, 683 Dementia with Lewy bodies (DLB), 655 Cytokines Dentate gyrus (DG), 511 EPO, 87–89 Derived CPECs (dCPECs), 509 G-CSF, 89 Desferrioxamine, 523 Cytokines and adhesion molecules Dexanabinol, 302, 303, 814 cells, 183 Dexanabinol (Pharmos), 105 ICAM-1, 184 Dexmedetomidine (Dex), 233 IL-1 and IL-6, 184 Dexpramipexole, 622 TNF-α, 184 Diabetes Cytoplasmic dynein, 612 and AD, 483, 484 DR, 711, 712 hypoglycemic coma, 709, 710 D ketoacidosis, 710, 711 Daclizumab (zinbryta), 690 Diabetic ketoacidosis, 710, 711 Dalfampridine Diabetic neuropathy MS, 683 cell therapy, 754 Dapsone, 535, 536 gene therapy, 754, 755 Decompression sickness (DCS), 699, 700 neuroprotection, 754 Decompressive craniotomy (DC), 825 Diabetic retinopathy (DR), 711, 712 Decompressive hemicraniectomy, 242 Diallyl trisulfide (DATS), 622, 623 Deep brain electrical stimulation (DBS), 320 DIAN-TU (Dominantly Inherited Alzheimer Deep brain stimulation (DBS) Network-Trials Unit) trial, 514 cortico-basal ganglia-thalamo-cortical Dichloracetate, 738 loop, 424 Dimebon effects of high-frequency, 424 AD, 540, 542 firing patterns, 424 Dimethyl fumarate, 683, 684 frequency stimulation, 424 Dipeptide-repeat proteins (DPRs), 638 glial-neuronal interactions, 424 Disease-associated microglia (DAM), 485 neural restoration, 424 DJ-1 gene, 408, 409 striatal reinforcement, 424 DNA binding drugs, 70 Dehydroascorbic acid (DHA), 505, 506 DNA repair enzymes, 19, 20 Dehydroepiandrosterone (DHEA), 154 Docosahexaenoic acid (DHA), 14, 207, 312 Delayed cerebral ischemia (DCI), 822 AD, 551 Delayed damage, 287 Donor skin cells, 633 Delayed postanoxic demyelination, 731 Dopamine (DA), 589, 602 Delayed post-hypoxic leukoencephalopathy and AD, 481, 482 (DPHL), 733, 734 Dopamine (DA) systems, 293 Delta-opioid receptor (DOR) agonists Dopamine receptors (DARs), 602 FK960, 91 Dopamine-induced hypertension, 822 gene therapy, 91, 92 Dopaminergic (DA), 414 hibernation, 90, 91 Double-strand DNA breaks (DSBs), 478, 479 mammalian cortical neurons, 90 Doxycycline, 434 strategies, 90 DP-b99 (D-Pharm), 256 Dementia Drug-induced hearing loss, 749 age-related, 648–652 Drug-resistant epilepsy AIDS, 655, 656 MCs, 663 autologous stem cells, 511, 512 Drug-resistant partial epilepsies, 661 Index 837

Drugs, inappropriate calcium release, 593, 594 Estrogen receptors (ERs) dsDNA breaks, 478, 479 AD Dysmyelinated mutant mouse model, 676 SERMs, 542, 543 ligands, 107 modulators, 108, 109 E Etanercept, 502, 503 Edaravone, 623 Evoked potentials (EPs), 808 Eicosapentaenoic acid (EPA), 594 Excitatory amino acid transporter (EAAT) Electrical fields, 160 family, 14 Electroconvulsive (ECS) therapy, 59 Excitatory amino acid transporter 2 Electroconvulsive therapy (ECT), 739 (EAAT2), 621 Electroretinogram (ERG), 790 Excitotoxicity, 408, 588 Embryonic stem cells (ESCs), 357 Experimental autoimmune encephalomyelitis remyelination, 677 (EAE), 667, 679, 681, 769, 772 Encephalopathy, 718 Experimental oral vaccines, 253 Endocannabinoids, 103 Extracellular serine protease thrombin, 15 Endoplasmic reticulum (ER), 480, 634 Extracellular superoxide dismutase Endothelial progenitor cells (EPCs), 754 (EC-SOD), 724 Environmental enrichment, 161 Extracellular vesicles (EVs), 318 Enzymatic antioxidants, 13 Ephrin-A5 blockers, 207 Epicatechin (EC), 210 F Epidemiology Failed clinical trials PD, 405 Ancrod, defibrinogenating agent, 260 TBI, 284 Aptiganel hydrochloride (cerestat), 261 Epigenetic dysregulation causes of, 267, 268 AD, 482, 483 Cerovive (disufenton sodium, Epilepsy AstraZeneca’s NXY-059), 261, 262 AEDs, 658, 660 Citicoline (Cytidine-5'-diphosphocholine), cell therapy, 661–662 262, 263 drug-resistant, 663 clinical vs. preclinical studies, 330 gene therapy, 663, 664 Desmoteplase (Lundbeck AS), 263, 264 HA, 664 erythropoietin, 264 hypothermia, 665 extensive prognostic analysis, 331 KD, 665 Gavestinel, 266 miR-211, 665, 666 improvements, 330, 331 neuronal damage mechanisms, 657, 658 Lubeluzole, 265 neuroprotection vs. sequelae of seizures, 658 multiple treatment strategies, 331 Epileptogenesis, 659, 660 Nalmefene, 265 Erythropoietin (Epo), 87–89, 303, 623, 750, Nimodipine, 266 751, 780, 816 NMDA receptor antagonists, 329 MS, 684 preventive measures, 269 Erythropoietin receptor (Epo-R), 780 Selfotel (CGS 19755, Novartis), 264 Estrogen shortening trial time, 331 AD, 542, 543 Sipatrigine, 266 E2-treated female myeloid-specific ER subgroup analysis, 330 alpha knockout mice, 208 therapeutic agents, 329 endogenous and exogenous, 207 Familial AD (FAD), 482, 483 estradiol replacement therapy, 208 Familial dysautonomia (FD), 387 free radicals, 208 Fcγ receptor-mediated phagocytosis, 556 neuroprotection, 109 Fetal alcohol syndrome (FAS), 722 post-ischemic inflammatory responses, 208 Fetus and neonate protective effects, 209 brain insults, 725 SERMs, 209 food deprivation, 725 838 Index

Fetus and neonate (cont.) Galantamine, 654 gene dysregulation, 725 Galantamine-induced Aβ clearance, 512 HI injury, 726–730 Gambogic amide, 125 hypothalamus, 725 Gangliosides, 370 preterm babies, 725, 726 Gantenerumab, 513, 514 Fever Gaseous anesthetics cooling the brain, 718 isoflurane, 805, 806 definition, 715 xenon, 806, 807 hyperthermia, 716 Gaseous microembolization, 815 infants and children, 715 GDF11 protein neurologic disorders, 716 AD, 553, 554 neurotransmitters, 716 GeneChip assay, 109 pharmacologic approaches, 717, 718 Gene recombination process, 537 systemic and neurological disorders, 716 Gene therapy, 91, 92, 793, 794 temperature, 715–717 AD FGF2 gene transfer molecular medicine, 516 AD, 518 NGF, 516–520 Fibroblast growth factors (FGFs), 120, 220, 349 NTFs, 516 Fingolimod, 594, 595 diabetic neuropathy, 754, 755 AD, 544, 545 epilepsy, 663, 664 MS, 684, 685 MS, 686, 687 FK506-binding protein 52 (FKBP52), 522 PD Flavones bFGF, 436 epicatechin (EC), 210 classical dopamine replacement, 436 isorhamnetin, 210 direct gene transfer into striatal cells vs. Fluid percussion injury (FPI), 323 cell transplantation, 437 Flupirtine, 771 GDNF, 438 FMS-like tyrosine-3 (FLT-3), 688 nigrostriatal pathway, 436 Folic acid, 559, 560 PNS, 752 Forkhead box O3A (Foxo3a), 600 SCI Fragile X syndrome (FXS) BDNF, 361 synaptopathies, 648 NGF, 361 Frataxin (FXN), 388 NT-3, 361, 362 Free radical scavengers, 595 NTFs, 361, 362 PD SNL, 746, 747 antioxidants, 435 TBI, 319 diapocynin, 435 Gene therapy, HD, 604 MAPT gene, 435 Gene vaccination, 520 tea extraction, 435, 436 Genetic disorders FREEDOMS (Fingolimod Research Batten disease Evaluating Effects of Daily Oral cerliponase alfa, 386, 387 therapy in Multiple Sclerosis), 685 CLN2, 385 Friedreich ataxia (FA), 388 FA, 388 Frontotemporal dementia (FTD), 383, 384, 610 FD, 387 Fusokine (GIFT15) Leigh syndrome, 389 MS, 685, 686 LSDs, 385 Niemann-pick type C (NP-C), 389, 390 PPT1, 386 G SBMA, 390, 391

GABAA, 805 SMA, 391, 392 GABAB, 805 SMN protein, 392 Gacyclidine, 343 Genomic Translation for ALS Clinical Care GADD34 upregulation, 11 (GTAC), 637 Galanin, 664 Genomics/proteomics, 589, 590 Index 839

Geographic atrophy (GA), 786 Granulocyte-macrophage colony-stimulating Geographic Atrophy Treatment Evaluation factor (GM-CSF), 221 (GATE), 790 AD, 543 Geroneuroprotectors (GNPs), and IL-15, 685, 686 650, 651 Gut microbiota, 9 Ginkgo biloba, 528, 529 Ginkgo biloba extract (GBE), 528, 529 Ginkgolides, 528 H Glatiramer acetate, 93, 624, 671, 697 Hearing loss Glaucoma causes, 743 aminoguanidine, 775 pathomechanism, 743, 744 antiglutamate agents, 776 prevention and treatment betaxolol, 776 drug-induced hearing loss, 749 glaucomatous optic neuropathy, 774 HBO, 745 IOP, 774 pharmaceutical approaches, 747, 748 neuroprotective approaches, 774 SCs therapy, 745, 746 NGF eye drops, 777 SNL, 746, 747 NMDA receptors, 774 strategies, 744 RGCs, 774 Heat shock protein 70 (Hsp70), 441 targeting Aβ, glaucoma treatment, 777 age-related dementia, 649, 650 TNF-α blocker, 777 Heat shock proteins (HSPs), 22, 105, 183 Glial cell line-derived neurotrophic factor Hematopoietic stem cell transplantation (GDNF), 120, 221, 375 (HSCT) Glial growth factor (GGF2), 693 MS, 678 Glial-restricted precursor cells (GRPs), Hematopoietic stem cells (HSCs), 317, 632 361, 511 Heme, 487 Globins, 15 Heme oxygenase (HO), 84 Glucagon-like peptide (GLP), 93 Hemoglobin-based oxygen carriers Glucagon-like peptide-1 (GLP-1), 209 (HBOCs), 142 Glu-R5, 614 Hepatic encephalopathy, 712, 713 Glutamate antagonists Heritable risk factors, 667 AD Herpes simplex virus vectors, 663 memantine, 520, 521 Herpes simplex virus-1 (HSV-1), 536, 663 blood glutamate scavenging, 95 Highly active antiretroviral therapy excitatory neurotransmitter, CNS, 94 (HAART), 655 families, 94 Histamine H2-receptor modulation, 212 pharmaceutical neuroprotective drug Histone acetylation (HAT) activity, 595 development activity, 94 Histone deacetylase (HDAC) inhibitors, 388, transporters, 95, 96 551, 596, 631 Glutamtergic dysfunction, 612 Histone deacetylase (HDAC)-based Glycine-proline-glutamate analogs therapeutics, 211 endogenous neuroprotective Histone deacetylase 4 (HDAC4), 410 tripeptide, 97 Histone deacetylase inhibitors (HDACis), 106, Trofinetide, 97 304, 397 Glycogen synthase kinase (GSK)-3α, 545 Historical development, 3 Glycogen synthase kinase (GSK)-3β, 545 Homocysteine (Hcy), 628 Glymphatic system, 6 Homophilic binding, 471 GM-1 ganglioside, 343 Hormones GM604, 625 estrogen and progesterone, 107 Golgi stress, 593 Human albumin, 822 GORE Flow Reversal System, 823 Human amyloid precursor proteins G-quadruplex (G4), 614 (hAPP), 484 Granulocyte colony-stimulating factor Human antibody (G-CSF), 89, 220 myelin, 692 840 Index

Human brain endothelial cells (HBMECs), 536 hearing loss, 745 Human embryonic stem cell (hESC), 355 PNS, 751, 752 Human immunodeficiency virus-1 (HIV-1) therapy, 144, 237, 238, 320 infection, 380 Hyperexcitability, 662 Human NEP (hNEP), 519 Hypertension Human neural progenitor cells (hNPCs), 792 prevent dementia, 709 Human pluripotent stem cell-derived neurons Hypertensive encephalopathy, 708, 709 (hPSC), 432 Hypoglycemic coma, 709, 710 Huntexil™, 598 Hypoglycemic shock/coma, 709 Huntingtin-associated protein (HAP-1), 589 Hypothermia, 321, 728 Huntingtin protein (HTT), 601 hypoxia-ischemia (HI), 163 Huntington's disease (HD) ketogenic diet, 164 antipsychotic D2 and 5-HT1A limitations, 162 antagonists, 591 Mediterranean diet, 165 antisense therapeutics, 604, 605 mild, 162 caspase inhibitors, 591 status epilepticus, 665 cell therapy techniques, 162 cell transplantation, 602–604 Hypothermia blankets, 718 combinatorial therapies, 602 Hypoxemic-ischemic encephalopathy, 700 cysteine and neuroprotection Hypoxia-inducible factors (HIFs), 22, 782 (see Cysteine and neuroprotection) Hypoxia-inducible factor-1 (HIF-1), 780 EPA, 594 Hypoxic-ischemic (HI) brain injury fingolimod, 594, 595 characterization, 726 free radical scavengers, 595 HBO therapy, 727, 728 gene therapy, 604 hypothermia, 728 HDAC inhibitors, 595, 596 management, 726, 727 inappropriate calcium release, drugs, melatonin, 728 593, 594 minocycline, 728 management (see Management) neuroprotection, 727 mhtt, 594, 601 nicotinamide mononucleotide adenylyl NTFs, 604 transferase 1, 729 pathomechanisms, 591 nitric oxide inhalation, 729 pathophysiology (see Pathophysiology) PAI-1, 729, 730 PDEs, 596 pathomechanism, 726 polyQ aggregation inhibitors, 596, 597 rEPO, 730 pramipexole, 597 Hypoxic-ischemic brain injury (HIBI), 25 pridopidine, 598 RNAi-based therapies, 605, 606 RRAS signaling pathway, 598 I sFV antibodies, 599 Ibudilast, 671 simvastatin, 599 MS, 687 SIRT1 activators, 599, 600 Idiopathic NPH (iNPH), 702 SIRT2 activators, 600 IGF-1, 693 stem cell-based therapy, 603 Imatinib, 673 synaptic activation, NMDA receptors, 600 Immune system, 18 targeting multiple pathways, 602 Immunogenicity, 557 tetrabenazine, 601 Immunosuppressive effect, 303 Hyaluronan (HA) In vitro assays, 31 preservation, brain ECS volume, 664 Induced pluripotent stem cells (iPSCs), 357, Hydrocephalus, 701, 702 410, 603, 636, 794

Hydrogen sulfide (H2S) Inducible nitric-oxide synthase (iNOS), 775 description, 97 Inosine, 212 hibernation, 98 Insulin Hyperbaric oxygen (HBO), 727, 728, 815 and AD, 483, 484, 538 Index 841

Insulin degrading enzyme (IDE), 483 K Insulin, neuroprotective effect, 109, 110 KAI subunit, kainate receptor, 96 Insulin-like growth factor (IGF), 121, 483, Kearns-Sayre syndrome, 738 625, 626 Ketamine, 805 Insulin-like growth factor-1 (IGF-1), Ketogenic diet (KD), 164, 626, 665 213, 222 Ketone bodies, 215 Integrated stress response (ISR), 304 KIFAP3, 614 Intensive care units (ICUs), 809 Kinase inhibitors Interferon beta-1a (IFNβ1a) MS, 688 AD, 545 Kinesin family member 5A (KIF5A), 614 Interferon-beta (IFN-β), 686 KL1333, 738, 739 Interferons, 671 Klotho treatment, 651 Interleukin-1 (IL-1), 64, 184 Kynurenine (KYN) inhibitors, 113 Interleukin-6 (IL-6), 184 Interleukin-10 (IL-10), 345 Intracellular adhesion molecule-1 L (ICAM-1), 184 Ladostigil tartrate, 546 Intracerebral hemorrhage, 190 Lamotrigine, 535, 772 Intracerebroventricular (ICV), 603 Laquinimod Intracranial aneurysms, 818, 819 MS, 688, 689 Intracranial pressure (ICP), 296 Late-onset Alzheimer's disease (LOAD), 494 Intraocular pressure (IOP), 774 Lenalidomide, 626, 627 Intravenous immunoglobulin (IVIG) Leukocyte adhesion inhibitors, 113, 114 treatment, 213 Levetiracetam (LEV), 324, 535 Intravenous immunoglobulins (IVIG) Levodopa, 417, 420–422, 438, 439, 443, 451 MS, 688 Levosimendan, 304, 305 Ion channel dysfunction, 181 Lewy body dementia (LBD), 655 Ion channel modulators Lidocaine, 807, 812 calcium channel blockers, 110 LINGO-1, 676 description, 110 Lipid metabolism Ziconotide (Prialt), 111 AD, 481 IPLEX, 626 Listerin, 611 Iris pigment epithelial (IPE), 781, 790 Lithium, 627 Iron chelation, 398 AD, 545 Iron chelators Liver disorders MS, 687, 688 bilirubin encephalopathy, 713, 714 Iron homeostasis, 407 hepatic encephalopathy, 712, 713 Ischemia-reperfusion (I/R) injury Liver X receptor (LXR) agonist, 786 aminoguanidine (AG), 232 Liver X receptor β (LXRβ), 441 dexmedetomidine (Dex), 233 Living brain slices, 33, 34 methylene blue (MB), 233 Lysosomal storage diseases (LSDs), 385 neuroprotection, 241 spin trap agents, 234 Ischemic preconditioning (IPC), 214, 215, M 779, 780 Macugen, 785 Ischemic stroke, 192 Macular degeneration ISF Aβ levels, 494 AMD, 782, 783 Isoflurane, 805, 806 antiangiogenic agents Isorhamnetin, 210 aflibercept, 784, 785 Istradefylline, 427 clinical trials, 784, 785 Macugen, 785 ranibizumab, 784 J cell therapy (see Cell therapy) JNK1-deficient CNS myeloid cells, 672 combining stem cell, gene therapies, 794 842 Index

Macular degeneration (cont.) Memantine, 520, 521, 601, 654 epidemiology, 782, 783 Mental stress, 27 gene therapy, retinal degeneration Mesencephalic-astrocyte-derived neurotrophic AMD, 793 factor (MANF), 446 combining stem cell, gene therapies, 794 Mesenchymal stem cells (MSCs), 303 primary photoreceptor diseases, 793 autologous adipose tissue, 510 RetinoStat®, 794 Metabolic stress, 588 LXR agonists, 786 Metabotropic glutamate (mGlu) receptors, 103 NTFs (see Neurotrophic factors (NPFs)) Metals nutritional protection, AMD, 788 and AD, 492, 494 oxidative-stress-induced apoptosis, 789 Meteorin (NsGene), novel neurotrophic pathomechanism, AMD, 783 protein, 126 progestogenic hormones, 788, 789 Metformin retinal degeneration, 786 AD, 538 RNAi-based treatments, AMD, 795 Methylcobalamin, 628 sulindac, 789 Methylene blue (MB) tandospirone, 790 AD, 546, 547 treatment, AMD, 783, 784 mitochondrial dysfunction, 736, 737 Magnetic resonance imaging (MRI), 36 Methylprednisolone, 346, 347 Malignant hypertension, 768 Microglias, 612, 613 Mammalian target of rapamycin (mTOR), and AD, 485 314, 547 MicroRNAs (miRNAs) regulation, 252 Management Microtubule-associated protein tau AD, 498, 499 (MAPT), 435 HD, 590 Mild cognitive impairment (MCI) PD AD, 576, 577 dopamine therapy limitations, 417, 419 non-dementia, 576 therapeutic interventions, 417 non-pharmacological approaches, 578 SCI pharmacological approaches, 577, 578 neuroprotective and regenerative Mild TBI (mTBI), 284 approaches, 341, 362 Milwaukee protocol, 706 TBI Mineralocorticoid receptor (MR) cerebral edema, 295, 296 activation, 216 classification, 294 Minocycline, 305, 306, 707 corticosteroids, 297 HI brain injury, 728 decompressive craniectomy, 297 MS, 689 intracranial pressure, 295 miR-211, 665, 666 pharmacological and non- Mitochondria-associated membranes pharmacological approaches, 295 (MAMs), 480 MAO-B inhibitors Mitochondrial DNA (mtDNA), 416 AD, 546 Mitochondrial dysfunction Masitinib, 628 encephalopathies, 737–739 Matrin-3, 614 energetic and oxidative, 735 matrix metalloproteinase (MMP) expression, malfunctioning, 735 66, 346 MB, 736, 737 Medial ganglionic eminence (MGE) cell MPT, 735, 736 grafting neuroprotection, 736 MS, 679 permeabilization, 735 Mediterranean diet, 165 respiration, 735 Medium spiny neurons (MSNs), 601, 603 Mitochondrial encephalopathies Melatonin, 441, 442, 506, 628 cell destruction, 738 HI brain injury, 728 dichloracetate, 738 MS, 689 Kearns-Sayre syndrome, 738 Melatonin receptor 1A (MT1), 628 MELAS syndrome, 738 Index 843

neuroprotection, 738, 739 antioxidants, 675 pathophysiology, 737 antisense and RNAi approaches, regulating pathways, 738 675, 676 TYMP mutations, 738 BBB, 694 Mitochondrial encephalopathy-lactic BCDT, 676 acidosis-stroke-like episodes cell therapy, 676–680 (MELAS) syndrome, 738 cladribine, 681, 682 Mitochondrial energy metabolism curcumin, 682 AD, 480 cyclophilin inhibitors, 682 Mitochondrial neurogastrointestinal cytokine-directed therapies, 682, 683 encephalopathy (MNGIE), 738, 739 dalfampridine, 683 Mitochondrial permeability transition (MPT), dimethyl fumarate, 683, 684 735, 736 erythropoietin (Epo), 684 Mitochondrial respiration, 735 fingolimod, 684, 685 Mitochondria-targeted antioxidants, 81 fusokine (GIFT15), 685, 686 Mitoxantrone, 671 gene therapy, 686, 687 Modafinil, 114 human antibody, 692 Monitoring of CNS function ibudilast, 687 cerebral, 807 iron chelators, 687, 688 EPs, 808 IVIG, 688 MEPS, 808 kinase inhibitors, 688 MIOM, 808 laquinimod, 688, 689 scoliosis surgery, 808 MAb, 690, 691 Monoclonal antibody (MAb), 556 melatonin, 689 Aβ removal minocycline, 689 crenezumab, 512, 513 neurotrophic factors, 692, 693 gantenerumab, 513, 514 nimodipine, 693 solanezumab, 514 oral immunomodulatory agents, 694 MS protein kinase Cβ, 694 alemtuzumab (lemtrada), 690 remyelination, 692 CD3+CD20 T cells, 690 RTLs, 694, 695 daclizumab (zinbryta), 690 statins, 695 indirect evidence, 690 teriflunomide, 696 natalizumab (tysabri), 690, 691 tolerance-directed immunotherapy, ocrelizumab, 690 696, 697 ofatumumab, 691 autoimmune inflammation in brain, Monophosphoryl lipid A (MPL), 557 671–673 Mossy cells (MCs) CD4+ T cell, 697 drug-resistant epilepsy, 663 characterization, 666 Motor Evoked Potentials (MEPS), 808 clinical trials, 671 Motor neuron (MN), 616 epidemiology, 666 MSCs-derived exosomes glatiramer acetate, 697 effects, 318 imatinib, 673 EVs, 318 management, 667, 668 Multi-infarct dementia, 653 natural killer cells, 697 Multimodal evoked potentials (MMEPs), 677 neuroprotective therapies, 668, 670 Multimodel intraoperative monitoring pathomechanisms, 668 (MIOM), 808 pathophysiology, 667 Multi-omics approach, ALS, 637 primary progressive, 666 Multiple endovascular modalities, 244, 245 relapsing remitting, 666 Multiple sclerosis (MS), 768 remyelination, 674 agents secondary progressive forms, 671 angiotensin-II inhibitors, 674, 675 TRPM4 cation channel blockers, 673 antiglutamate, 675 Multiple system atrophy (MSA), 656, 657 844 Index

Multipotential neuroprotective agents, 306 herbal preparations, 137 Muscimol, 805 nicotinamide, 138 Mutant human TDP-43 (mTDP-43), 634 punicalagin, 138 Mutant huntingtin (mhtt), 590, 594, 597, 601 resveratrol, 139 Myelin, 692 wogonin, 137 Myelin basic protein (MBP), 667, 676 NaVI.5, 677, 678 Myelin oligodendrocyte glycoprotein Near infrared laser (NIR) technology, 239 (MOG)-induced optic neuritis, 684 Near-infrared spectroscopy (NIRS), 815 Myelin-associated glycoprotein (MAG), 351 Neotrofin (AIT-082), 533 Myelin-associated inhibitory factors Neprilysin (NEP) (MAIFs), 342 in Aβ degradation, 474 Myelin-oligodendrocyte glycoprotein-induced gene therapy, 518, 519 experimental autoimmune Nerve growth factor (NGF), 122, 532 encephalomyelitis (MOG-EAE), 674 AD Mylinax, 681 advantages, 517 Myocardial infarction, 707, 708 and MMSE, 517 clinical testing, 517 FGF2 gene transfer, 518 N gene vaccination, 520 N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2- NEP, 518, 519 oxopiperidine-3-carboxamide neurodegenerative disorders, 520 (HIOC), 788 nucleus basalis of Meynert, 517 N-2-mercaptopropionyl glycine, 218 patient's skin, 517 n-3 fatty acids (FA) triglyceride (TG) pharmacologic therapy, 517 emulsions, 223 phase I trial, 517 Na+ channel blockers, 112 prevents/reduces cholinergic neuronal NAALADase inhibitors, 101 degeneration, 518 N-acetylaspartate (NAA), 625 retroviral vectors, 517 N-acetylserotonin (NAS), 787 viral gene transfer, APPsα, 519 NADPH oxidase type 4 (NOX4) inhibitors, 223 Nerve growth factor receptor (NGFR), 340 N-alkylglycines, 102 Neural grafting, 662 Nanobiotechnology-based therapeutics Neural precursor cells (NPCs), 430 AD MS, 680 BBB, 530 Neural stem cells (NSCs), 385, 431, 614 disadvantages, 530 AD molecular motors, 530 autologous stem cells, dementia, nanobodies, 530, 531 511, 512 selegiline-PEG nanoparticles targeting BDNF, 511 Aβ fibrils, 531 grafting, 511 vitamin E, 531 neuronal differentiation, 510 Nanobodies, 530, 531 transplantation, 510 Nanosweeper, 515 astrocytic phenotypes, 358 Nasal delivery, 217 axonal regeneration, 359 Natalizumab, 690, 691 genetic fate mapping, 358 Natural killer cells, 697 grafting, 359 Naturally-derived compounds restoration of motor function, 359 American and Asian species of ginseng, 137 VPA, 359 cinnamon, 133 Neural stem/progenitor cells (NSCs/NPCs), 603 coffee consumption, 134 Neuregulin, 686 creatine (creatine monohydrate), 134 Neuregulin-1 (NRG-1), 222 curcumin, 135 Neurite outgrowth-promoting agents flavonoids, 136 monoclonal antibodies, 115 glyceryltriacetate (GTA, Triacetin), 136 Neuritic plaques green tea, 136 AD, 469, 470 Index 845

Neurocognitive sequelae, 291, 292 anti-NMDA receptor (NMDAR) Neurodegeneration encephalitis, 698 and AD, 490 cardiac arrest, 732, 733 Neurodegeneration Consortium CNS infections, 703–707 (NDC), 373 CO poisoning, 730 Neurodegenerative disorders CSF circulatory disorders, 701–702 Creutzfeldt-Jakob disease (see Creutzfeldt- DCS, 699, 700 Jakob disease) dementia, 648–656 dementia (see Dementia) DPHL, 733, 734 genetics (see Genetic disorders) epilepsy (see Epilepsy) glutamate-based therapies, 397 fetus and neonate, 725–730 HDACis, 397, 398 hearing loss, 742–749 iron chelation, 398 mitochondrial dysfunction, 735–739 mitochondria permeability transition pore MS (see Multiple sclerosis (MS)) complex, 398, 399 MSA, 656, 657 pathomechanism (see Pathomechanism) PNS (see Peripheral nervous system (PNS)) proteostasis modulation, 399 psychiatric disorders, 739–742 Neurofibrillary tangles (NFTs), 499 sleep apnea, 734, 735 AD, 469, 470 synaptopathies, 647–648 Neuroimmunophilin ligands systemic disorders, 707–718 calcium-dependent signal transduction therapeutic radiation, 723–725 pathway, 115 TM, 698, 699 cyclosporin-A, 116 toxic encephalopathies, 718–723 description, 115 victims of drowing, 700 immunosuppressant FK506 Neuronal loss, 469 (tacrolimus), 116 Neuron-restrictive silencer factor (NRSF), rapamycin, 117 554, 649 Neuroinflammation, 288, 289 Neuropeptide galanin expression, 15 AD Neuropeptide Y (NPY), 664 amyloid deposition, 485 Neuroprotectin, 789 autotoxicity, 485 Neuroprotection etanercept, 502, 503 in AD (see Alzheimer's disease (AD)) glial activation, 486 ALS (see Amyotrophic lateral sclerosis IL-12 and IL-23, 486 (ALS)) microglia and astrocytes, 485 anesthesia and surgery (see Anesthesia and and NO, 486, 487 surgery) NSAID indomethacin, 485 HD (see Huntington's disease (HD)) NSAIDS, 503, 504 neurological disorders (see Neurological and oxidative stress, 489, 490 disorders) PPARgamma, 504 optic nerve (see Optic nerve) BBB dysfunction, 26 PD (see Parkinson's disease (PD)) biomarkers, 26 Retina (see Retina) description, 26 SCI (see Spinal cord injury (SCI)) fibrinogen, 26 TBI (see Traumatic brain injury (TBI)) microglia, 26 Neuroprotective agents receptors, 26 AD synaptic pruning, 26 cerebrolysin, 528 Neuroinflammation inhibitors ginkgo biloba, 528, 529 AD tetrahydrocannabinol, 529, 530 ceramide, 544 Neuroprotective drug discovery, 30 CSP-1103, 544 Neuroprotective effect fingolimod, 544, 545 AD IFNβ1a, 545 antidiabetic drugs, 537–539 Neurological disorders, 27 antiepiletic drugs, 535 846 Index

Neuroprotective effect (cont.) high-dose human albumin therapy, 255 antihypertensive drugs, 539, 540 insulin-like growth factor, 625, 626 antimicrobial drugs, 535, 537 KD, 626 bexarotene, 540 lenalidomide, 626, 627 dimebon, 540, 542 lithium, 627 estrogen receptors, 542, 543 masitinib, 628 lithium, 545 melatonin, 628 MAO-B inhibitors, 546 methylcobalamin, 628 MB, 546, 547 mildronate, 257 neuroinflammation, 543–545 MS, 668, 670 rapamycin, 547 NaPB, 631 saracatinib, 547, 548 olesoxime, 629 testosterone, 548 ONO-2506, 629 valproic acid, 549 PD PD adenosine A2A antagonists, 427 DJ-1 protein, 443, 444 adenosine A2A receptor, 427 LRRK2 mutation, 443 antiapoptotic strategies, 427, 428 pramipexole, 420, 421 ATP13A2 activation, 428 rasagiline mesylate, 421, 422 CDNF, 434 rivastigmine treatment, 423 cell therapies (see Cell therapies) ropinirole, 422 clinical measures, 420 selegiline mechanisms, 423 clinical trials, 455 Neuroprotective gene expression, 11 CML treatment, 443 Neuroprotective strategies cogane™, 433 PD CSF, 443 ALDH1A1, 415 dopaminergic deficits characteristics, 427 Cav1.3 Ca2+ channels, 413 doxycycline, 434 dysfunctional mitochondria, 416, 417 evaluation, 458 genetic animal model, 414, 415 free radical (see Free radical pacemaking mechanisms, 413 scavengers) RNAi screening, 415, 416 GBA1 mutations, 428, 429 α-synuclein aggregation, 416 gene therapy (see Gene therapy) Neuroprotective therapies Hsp70, 441 AIMSPRO, 619 istradefylline, 427 Anakinra, 619 L-type Ca2+ channels, 429 antisense therapy, 620 LXRβ, 441 APC, 617, 619 melatonin, 441, 442 arimoclomol, 620, 621 9-methyl-β-carboline, 426 ceftriaxone, 621 MPTP toxicity, 427 CoQ10, 621 neurodegenerative process, 419, 420 COX-2, 621, 622 nicotine, 442 DATS, 622, 623 nigrostriatal dopaminergic pathway dexpramipexole, 622 degeneration, 454, 455 DP-b99 (D-Pharm), 256 nilotinib, 442, 443 edaravone, 623 Nrf2, 448 Epo, 623 Nurr1 free radical scavengers, 255, 256 RXRα activation, 448 gene therapy omega-3 (n-3) PUFAs, 448, 449 AAV-IGF1, 624 pro-apoptotic protein Bax, 453 gene editing, 624 RAB3B overexpression, 449 neural progenitor cells, 624 resveratrol, 449, 450 RNAi, 624 RNAi therapy, 450 glatiramer acetate, 624 safinamide, 451 GM604, 625 sirtuin 2 inhibitors, 451, 452 Index 847

squalamine, 452 bFGF, 220 statins, 452, 453 BMPs, 118 α-Synuclein O-GlcNAcylation, 426 CDNF, 220 vitamin D, 453, 454 CNTF, 119 perindopril, ACE-inhibitor, 257 cortical and hippocampal neurons, 117 riluzole, 629, 630 FGF, 120 RNAi-based therapy, 630, 631 G-CSF, 220 stem cell therapy (see Stem cell therapy) GDNF, 120, 221 talampanel, 634 GM-CSF, 221 tamoxifen, 634 IGF, 121 vaccination, 635 IGF-1, 222 VEGF, 635 NAS, 787 vitamin E, 636 neuregulin-1 (NRG-1), 222 Neuroregeneration, 29 neurotrophins, 123 causes, 325 NGF, 122 classification, 326, 327 PD intrinsic factors, 325 BDNF, 436, 445 Neurorehabilitative strategies, 247 bFGF, 444 Neuroserpin (NSP), 218 GDNF, 436, 438, 439, 445, 446 Neurosteroids, 307 MANF, 446 Neurosurgery microdialysis studies, 447 arteriovenous malformations, 818 NTN, 446, 447 brain tumors, 823, 824 Parkin's E3-ligase activity, carotid endarterectomy, 822, 823 439, 440 cerebral angiography and endovascular PDGF, 447 surgery, 817 potential mechanisms, 444 cranioplasty, 825 SCI DC, 825 BDNF and NT-3, 340 HBO preconditioning (PC), 824, 825 bFGF, 340 intracranial aneurysms, 818, 819 CNS neurons, 349 ischemic preconditioning/tolerance, 824 FGFs, 349, 350 neurosurgical interventions, 824 mechanisms, 349 SAH neurons regeneration, 350 vasospasm, 819, 822 NGF, 340 Neurosurgical procedures NT-3, 349 chronic cerebral ischemia, 246 scientific problems, 186 decompressive hemicraniectomy, 242 stress-induced neuropsychiatric disorders, multiple endovascular modalities, 244, 245 741, 742 stenting, 244 stroke, role in, 185 thrombectomy, 243 TBI Neurotoxicity Bcl-2, 307 alcohol, 722, 723 bFGF, 292 Neurotrophic factors (NTFs), 12, 412, 602, 604 hypothermia, 307 AD IGF-1, 293, 307 AL-108, 532 NGF, 292, 307 BDNF, 532, 533 NNZ-2566, 307 deficiency, 532 uses, 307 limitations, 534 Neurotrophin-3 (NT-3), 349 Neotrofin (AIT-082), 533 NeurotrophinCell (NtCell), 431 p75NTR, 533, 534 Neurotrophins, 123 ADNF, 118 Neurovascular remodeling, 327 AMD, CNTF, 786 Neurturin (NTN), 446, 447 BDNF, 119 (see Brain-derived NF-E2-related factor (Nrf2), 448 neurotrophic factor (BDNF)) NGF eye drops, 777 848 Index

Nicastrin Non-pharmacological approaches APP, 475 hyperbaric oxygen therapy, 352 Nicotinamide, 311 hypothermia, 353 AD treatment, 551 MCI, 578 Nicotinamide mononucleotide adenylyl Non-pharmacological neuroprotective transferase 1, 729 therapies Nicotine, 442 HBO therapy, 237, 238 Nicotine and nicotinic receptor agonists, 128 hypothermia combination, 239 Nicotinic acetylcholine receptors hypothermia, acute stroke, 237 (nAChRs), 512 NIR technology, 239 Niemann-Pick type C (NP-C) disease, 389 preconditioning strategies, 240 Nilotinib, 515 Non-pharmacological preconditioning, Nimodipine, 654, 701 165, 166 MS, 693 Non-pharmacological strategies Nitric oxide (NO), 181 PD and AD, 486, 487 CR, 425, 426 donating derivatives, 131 DBS, 424 mimetics, 131 MPTP, 425 Nitric oxide synthase (NOS), 486 physical exercise, 425 Nitric oxide synthase inhibitors, 130 Non-rapid eye movement (NREM) sleep Nitrones, 82 disruption, 495 NitroSynapsin, 647 Nonsense-mediated decay (NMD) NMDA receptor ion channel complex pathway, 373 AMPAKINEs (RespireRx), 102 Nootropics annabidiol (CBD), 104 metabolic enhancers, 132 antagonists, 100 Piracetam, 132, 133 cytoprotective effects, glutathione, 105 properties, 132 damage mediated attenuation, excitatory Norepinephrine (NE), 293 amino acids, 99 Norgestrel, 788 dexanabinol (Pharmos), 105 Normal pressure hydrocephalus (NPH), 702 endocannabinoids, 103 Nortriptyline, 594 Gacyclidine (G-11), 101 Notch signaling, 748 glutamate binding sites, 98 NR4A nuclear orphan receptors, 11 Ifenprodil, 100 NSAIDS, 503, 504 Memantine, 101 NSC transplantation mGlu receptors, 103 demyelination, 679 NAALADase inhibitors, 101 Nuclear factor I-A (NFI-A), 16 N-alkylglycines, 102 Nuclear receptor-related 1 (Nurr1) NMRD NR2B subunits, 100 Retinoid X receptor α (RXRα) total receptor blockade, 99 activation, 448 NMDA receptors, 309, 612 Nuclear Respiratory Factor-1 NO-based strategies, 223 protein, 209 Nogo, 525 Nuclear-factor erythroid 2-related factor 2 Nogo-66 receptor 1 (NgR1), 342 (Nrf2), 622 Noise-induced hearing loss, 747 Nucleus basalis of Meynert, 517 Non-arteritic anterior ischemic optic Nutritional approaches neuropathy (NAION), 781, 782 AD Non-pharmaceutical approaches axona, 549, 550 TBI choline supplementation, 550 application of controlled vacuum, 322 cocktail of dietary supplements, 550 DBS, 320 DHA, 551 HBO therapy, 320, 321 nicotinamide, 551 hypothermia, 321 omega-3 fatty acids, 552 microglia migration, 321, 322 NVP015, 738 Index 849

O Oxidative injury model, 32 Obstructive sleep apnea (OSA), 734, 735 Oxidative stress, 588, 615 Ocrelizumab, 690 and AD, 489, 490 Ofatumumab, 691 age-related dementia, 649 O-GlcNAcylation, 426 etiology of PD, 411 Olesoxime, 629 free radical production, 411 Olfactory ensheathing cells (OECs), 677 Oxygen free radicals, 181 adult nasal lining, 354 Oxygen therapeutics autologous transplantation, 354 description, 141 cell grafting, 354 HBO therapy, 144 neurological improvement, 354 HBOCs, 142 trial protocol, 354 oxygen carriers, 142 Oligodendrocyte precursor cells (OPCs) PFCs, 143 demyelinating injuries, 355 Oxygen-induced retinopathy (OIR), 782 factors, 355 Oxygen-regulated protein 150 kD hESC, 355 (ORP150), 126 regulatory factors, 355 Oligodendrocytes, 616, 692 Omega-3 (n-3) polyunsaturated fatty acids P (PUFAs), 448 Pannexin channel blockers, 224 Omega-3 fatty acids Parkinson's disease (PD) AD, 552 DA neurons, 409 Omega-3 polyunsaturated fatty acids, 72 DJ-1 gene mutation, 408, 409 Oncomodulin, 773 DJ-1 mutation, 409 ONO-2506, 629 epidemiology, 405 Operation Brain Trauma Therapy (OBTT), 312 failed clinical trials, 455 Optic nerve gene therapy techniques, 436 glaucoma (see Glaucoma) genetic variability, 408 optic neuropathy (see Optic neuropathy) Lewy body formation, 408 trauma LRRK2 gene mutations, 410 regeneration, optic nerve, 773 management (see Management) Optic neuritis neuroprotection, 410 BMD, 770 neuroprotective effect (see Neuroprotective calpain activation, 769 effect, drugs) EAE, 769 neuroprotective strategies (see efficacy of drugs, 770, 771 Neuroprotective strategies) experimental therapies, 770 neuroprotective therapies (see flupirtine, 771 Neuroprotective therapies) resveratrol, 772, 773 non-pharmacological strategies (see RGC, 770 Non-pharmacological strategies) sodium channel blockers, 772 pathophysiology (see Pathophysiology) Optic neuropathy prevalence, 405 optic neuritis (see Optic neuritis) SEMA5A gene, 408 pathophysiology, 768 α-synuclein-induced neuropathology, 408 Oral immunomodulatory agents therapeutic strategies, 417 MS, 694 Passive immunization, MAbs, 556 Organophosphorus poisoning, 719, 720 Pathomechanism Osmotic diuretics AD mannitol, 140 Aβ deposits (see Aβ deposits) OPN, 141 APP (see Amyloid precursor protein Osteogenic protein-1 (OP-1), 123 (APP)) Osteopontin (OPN), 141, 824 body's homeostasis, 497 Oxidative damage brain metabolism, 480, 481 and aging, 76, 77 cerebral atrophy, 469 neurodegenerative disorders, 77 cognitive deficits, 484 850 Index

Pathomechanism (cont.) motor neurons interactions, cognitive impairment with aging, 496, 497 astrocytes, 615 components, 498 neurotrophic factors, 615 diabetes, 483, 484 nuclear pore impairment, 615 and dopamine, 481, 482 OD1, 615 epigenetic dysregulation, 482, 483 oligodendrocytes, 616 etiology, 497 oxidative stress, 615 fibrillar aggregates, 497 pathomechanisms, mutant SOD1, 616 functional role of genes, 482 protein aggregation, 617 insulin, 483, 484 retrograde axonal transport, 611 lipid metabolism in brain, 481 RNA metabolism abnormality, 616 microglia, 485 cerebral ischemia mitochondrial energy metabolism, 480 adenosine diphosphate, 179 neuritic plaques, 469, 470 calcium overload, 180 neurodegeneration, 490 cerebral edema, 182 and neuroinflammation, 485–490 cytokines and adhesion molecules neuronal loss, 469 (see Stroke) NFTs, 469, 470 DNA damage and repair, 185 and RNA-binding proteins, 470, 471 extracellular glutamate, 182 risk factors, 490–496 free radicals, 180 tau, 470 gene expression, 182 CO poisoning, 731, 732 HSP, 183 hearing loss, 743, 744 ion channel dysfunction, 181 HI brain injury, 726 nitric oxide (NO), 181 MS, 668 NTFs, 185, 186 neurodegeneration oxygen free radicals, 181 aging, 371 PAR1, 186 apoptosis role, 377, 378 PARP gene, 186 Cdk5, 372 HD CSPα, 372 amino acid metabolism, 589 exosomes, 373 apoptosis, 589 gangliosides, 370 DA, 589 genomic technology, 374 excitotoxicity, 588 glia role, 378 genomics/proteomics, 589, 590 metals role, 378 impaired phospholipid-related signal neural transport, 374 transduction, 589 neuroinflammation, 375 metabolic stress, 588 neurotrophic factors lack, 375 oxidative stress, 588 pluripharmacological properties, 371 polyglutamine and copper binding, 590 protein misfolding, 376, 377 optic neuropathy, 768 spread, 379 PD α-synuclein, 371, 372 apoptosis, 407 TDP–43 proteinopathy, 379 dopamine homeostasis, 406, 407 translation dysregulation, 373 excitotoxicity, 408 viral infections, 380–382 genes, 408–410 Pathophysiology HDAC4, 410 ALS, 610 iron homeostasis, 407 clumping, abnormal proteins, 610, 611 misfolding proteins, 412 FTD, 610 NTFs, 412 genetic factors, 613, 614 oxidative stress, 411 glutamate toxicity (excitotoxicity), 612 PrPC, 412, 413 immune-mediated mechanism, 612, 613 SV2C, 413 ion channel dysfunction, 613 α-synuclein, 407 mitochondrial dysfunction, 617 VMAT2, 406, 407 Index 851

SCI Peroxisome proliferator-activated receptor NTFs, 340 alpha (PPAR-α), 790 pathomechanism, 338 Peroxisome proliferator-activated receptor-γ secondary injury mechanisms, 338 (PPAR-γ), 225 TBI Peroxisome-proliferator-activated receptors axonal damage, 287, 288 (PPARs), 148 BBB damage, 289 PGC-1α elevation, 12 blast injury sequelae, 286 PGE2 EP2 receptor activation, 226 cerebral edema, 287 Pharmaceutical approaches CTE, 289–291 hearing loss, 747, 748 delayed damage, 287 Pharmacologic approaches genetics, 294 fever, 717, 718 genomic response, 289, 290 Pharmacologic neuroprotective agents immediate damage, 285 AEDs (see Antiepileptic drugs (AEDs)) neurocognitive effects, 291, 292 anesthetic, 196 neurodegeneration-related proteins, antiapoptotic, 196–198 293, 294 antidepressants, 198 neuroinflammation, 288, 289 anti-HMGB1 monoclonal antibody, 200 neurotransmitters, 293 antiinflammatory see( Antiinflammatory NTFs, 292, 293 agents) secondary injury mechanisms, 287 antioxidant approaches (see Antioxidant γ-secretase components, 293 approach) sequelae, 287 arimoclomol, 204 PD with dementia (PDD), 655 ASICs blockers, 195 Peptide nucleic acids (PNAs), 508 aspirin, 230 Peptides cardiac glycosides, 204 C3-derived, 145 clenbuterol, 204 CRH, 146 clopidogrel (Plavix), 230 (see also TRH, 146 Coagulation inhibitors) VIP, 146 curcumin, 206 Perfluorocarbons (PFCs), 143 dipyridamole, 231 Perioperative neuroprotection, 809 docosahexaenoic (DHA) acid, 207 Peripheral nervous system (PNS) ephrin-A5 blockers, 207 CIDP, 756 estrogen, 207, 209 (see Flavones) CMT1A, 757 GLP-1, 209 neuroprotection glutamate clearance from blood, 211 gene therapy role, 752 hamartin induction, 211 HBO role, 751, 752 HDAC-based therapeutics, 211 neurotrophic factors role, 752 hemorrhage prevention, 236 pharmacological approaches to histamine H2-receptor modulation, 212 Schwann cells, 752 IGF-1, 213 Schwann cell transplantation, 753 inosine, 212 WldS protein, 753 IPC, 214, 215 neuroprotective agents IVIG treatment, 213 ALCAR, 750 ketone bodies, 215 atorvastatin, 750 magnesium ion, 215 EPO, 750, 751 miR-223, 216 peripheral neuropathy, 753–756 MR activation, 216 Peripheral neuropathy, PNS N-2-mercaptopropionyl glycine, 218 chemotherapy-induced neuropathy, NA-1 (NoNO Inc), 217 755, 756 nasal delivery, 217 diabetic neuropathy, 754, 755 NeuroAiD, 218, 219 Peritumoral brain edema (PTBE), 824 NSP, 218 Perlecan domain V (DV), 224 NTFs (see Neurotrophic factors (NTFs)) 852 Index

Pharmacologic neuroprotective agents (cont.) p75 neurotrophin receptor (p75NTR), 533, 534 pioglitazone, 225 P7C3 compounds, 144 progesterone, 226 Poly(ADP-ribose) polymerase (PARP), 821 sildenafil (Viagra), 229 Poly(ADP-ribose) polymerase (PARP) statins, 228, 229 enzyme, 73 ticagrelor, 231 Poly(ADP-ribose) polymerase (PARP) Pharmacologic therapy, 517 gene, 186 Pharmacological approaches Poly(ADP-ribose) polymerase-1 (PARP-1) age-related dementia, 650, 651 inhibitors, 710 MCI, 577, 578 Polyethylene glycol (PEG), 305, 314 to Schwann cells, 752 Polyglutamine (polyQ) aggregation inhibitors, Pharmacological neuroprotective agents 596, 597 4-aminopyridine, 342 Polyglutamine Binding Peptide 1 (QBP1), antiexcitotoxic agents, 343 596–597 ChABC, 343, 344 Polymer nanoparticles, 40 DHA, 344 Polymorphonuclear leukocytes (PMNs), 288 free radical scavengers, 344, 345 Positron-emission tomography (PET), 35, 294 gacyclidine, 343 Postcardiac arrest syndrome, 707 GM-1 ganglioside, 343 Posterior reversible encephalopathy syndrome IL-10, 345 (PRES), 714–715 immunosuppressants, 345 Postoperative cognitive decline (POCD), 809 inflammatory response, 352 Post-stroke dementia, 653 macrophage responses, 348 Post-traumatic epilepsy (PTE), 323, 661 methylprednisolone, 346, 347 Post-traumatic stress disorder (PTSD), 290 minocycline, 347, 348 Potassium (K+) channels, 112 MMPs, 346 PPARgamma, 504 neurite growth inhibitors, 342 Pramipexole, 597 NgR1, 342, 343 a2 adrenoreceptors, 420 rhEPO, 344 levodopa-induced toxicity, 420 Rho antagonist, 350 mechanisms, 420, 421 Rho signaling pathway, 350 Preconditioning (PC), 815 selenium, 351 Preconditioning strategies, 240 sialidase, 351 Preproenkephalin, 507 TLRs, 348 Preterm babies, 725, 726 UA, 352 Pridopidine, 598 Pharmacological preconditioning, 147 Prion protein (PrP), 17, 412 Pharmacoresistant epilepsies, 662 Pro-apoptotic protein Bax, 453 Phenserine, 510 Pro-electrophilic drugs (PEDs), 83 AD, 501, 502 Progesterone receptors (PR), 308 Phenytoin, 772 Progestogenic hormones, 788, 789 Phosphatidic acid (PA), 428 Progressive multifocal leukoencephalopathy Phosphodiesterase (PDE) inhibitor (PML) AD, 552, 553 CNS infections, 704, 705 Phosphodiesterase (PDEs) inhibitors, 596 Progressive supranuclear palsy (PSP), 384 Physical exercise, 166, 651, 652 Proinflammatory mediators, 612 Pigment epithelium-derived factor (PEDF), Proliferative diabetic retinopathy (DR), 796 123, 790 Propofol, 314, 804, 805 Plasminogen activator inhibitor-1 (PAI-1), Prosaptide TX14, prosaposin-derived 729, 730 peptide, 127 Platelet derived growth factor Prostaglandin receptor antagonists, 67, 68 (PDGF), 447 Protease-activated receptor-1 (PAR1), Platelet-derived growth factor receptor-α 186, 617 (PDGFR-α) signaling, 673 Protein kinase C (PKC), 613 Plexxikon, 674, 688 Protein kinase C activators, 149 Index 853

Protein kinase Cβ Remyelination, 692 MS, 694 ESCs, 677 Protein misfolding MS, 674 amyloid formation, 376, 377 Renal disease, 714, 715 intrabodies target, 376 Renin angiotensin system (RAS), 674 molecular chaperones, 376 Reperfusion injury after cerebral ischemia, tau, 377 187 Proteins Repressor element 1-silencing transcription amyloid precursor, 148 factor (REST), 554, 649 protein kinase C activators, 149 Resveratrol, 506, 507, 748, 772, 773 riluzole, 149 Reticulon, 525 Proteoglycan-degrading enzymes, 227 Retina Proteomics, 21 DR Proteosome inhibitors, 227 RNAi-based approaches, diabetic Proton irradiation, 724, 725 retinopathy, 796 Psychiatric disorders macular degeneration (see Macular ECT, 739 degeneration) schizophrenia, 739, 741 OIR, 782 stress-induced neuropsychiatric disorders, retinal ischemia (see Retinal ischemia) 741–742 Retinal ganglion cells (RGCs), 769, 773, 774 Psychosocial stress Retinal ischemia and AD risk, 494 β-adrenoceptor antagonists, 778, 779 Purine nucleoside inosine, 126 BMD, 779 Putative genes, 294 Epo, 780 gene therapy, 781 hyperbaric oxygen, CRAO, 781 Q IPC, 779, 780 Quercetin, 83 NAION, 781, 782 thioredoxin, 782 Retinal nerve fiber layer (RNFL), 771 R Retinal pigment epithelium (RPE), 790 Rabies virus Retinopathy of prematurity (ROP), 796 CNS infections, 706 RetinoStat®, 794 Radiation encephalopathy, 723, 724 Retrograde axonal transport, 611 Radiation-induced hippocampal dysfunction Reverse transcriptase, 537 SOD, 724 Rho signaling pathway, 350 RAF1, 598 Ribosome-associated quality control, 611 Ragged-red fibers, 738 Riluzole, 629, 630 Rai adaptor protein, 17 Risk factors Raloxifene AD AD, 543 aging, 491 Randomized controlled trials (RCTs), 560 education level/type of job, 491, 492 Ranibizumab, 784 etiology and pathogenesis, 490 Rapamycin, 314, 315 metals, 492, 494 AD, 547 psychosocial stress, 494 Rasagiline mesylate, 421, 422 sleep deprivation, 494, 495 Reactive oxygen species (ROS), 323, 656 and TBI, 495, 496 catalase reduces mitochondrial, RNA-binding proteins 724, 725 and AD, 470, 471 Recombinant EPO (rEPO), 730 RNAi-based therapies, HD, 253, 605, 606 Recombinant human erythropoietin (rhEPO), RNA interference (RNAi), 150 344, 780, 820 MS, 675, 676 Recombinant T cell ligands (RTLs) Rosiglitazone MS, 694, 695 AD, 538, 539 Remacemide, 812 RRAS signaling pathway inhibition, 598 854 Index

S Sleep deprivation Safinamide, 451 AD, 494, 495 Saracatinib Small-molecule enhancers (SMER), 594 AD, 547, 548 Sodium phenylbutyrate (NaPB), 631 Sarin gas, 719, 720 Solanezumab, 514 Sartans, 715 Somatosensory evoked potentials (SSEPs), Schizophrenia 808, 815 cognitive impairment, 740, 741 Sphenopalatine ganglion neurostimulation, 246 neuroprotection, 739, 741 Spinal and bulbar muscular atrophy Schwann cells, 356 (SBMA), 390 pharmacological approaches, 752 Spinal cord injury (SCI) transplantation, PNS, 753 cell therapy (see Cell therapy) Secretase modulators clinical trials, 363 AD combined approaches, 362 Aβ peptide, 524 neuroprotective therapies, 363 inhibitors, β-secretase, 524–526 non-pharmacological approaches (see inhibitors, γ-secretase, 526–528 Non-pharmacological approaches) sAPPα, 524 pathophysiology (see Pathophysiology) Secretases pharmacological neuroprotective agents amyloid cascade, 474, 475 (see Pharmacological Selective estrogen receptor modulators neuroprotective agents) (SERMs) Spinal muscular atrophy (SMA), 391 AD Squalenoyl adenosine nanoparticles, 40 estrogen, 542, 543 Src family kinases (SFKs), 548 GM-CSF, 543 Statins, 152, 153 raloxifene, 543 MS, 695 Selective serotonin reuptake inhibitors Stem cell (SCs) therapy (SSRIs), 59 hearing loss, 745, 746 Selegiline-loaded PLGA-PEG nanoparticles, 531 Stem cell factor (SCF), 17, 18 Selegiline-PEG nanoparticles targeting Stem cell therapy Aβ fibrils autologous hematopoietic stem cells, 632 AD, 531 clinical applications, 631 SEMA5A gene, 408 drug discovery, 633 Semagacestat, 527 intrathecal injections, MSCs, 632 Semipermeable polymers, 661 intrathecal NSCs, 632 Sensorineural hearing impairment, 743 suppressors, mTDP-43 toxicity, 634 Sensorineural hearing loss (SNL), 746 Stem cell transplantation, 791, 792 gene therapy, 746, 747 AD Serotonin 5-HT1A (5-HT1A) receptors, 591 autologous adipose tissue derived Seven conserved proteins (SIRT1-7), 152 MSCs, 510 Siagoside, monosialoganglioside clinical trials, 510 (GM1), 127 NSCs, 510–511 Sigma receptor agonists, 151 Stem cells Simvastatin, 315, 599 BM, 357 Single photon emission computed tomography cholinergic neurons transdifferentiation, 360 (SPECT), 35 ESC therapy, 357 Single-chain Fv (sFv) antibodies, 599 ESC transplantation, 357 Single-stranded (ss), 605 evaluation, 360, 361 Sinking skin flap (SSSF), 825 human dental pulp transplantation, siRNAs, 605, 795 359, 360 SIRT1 activators, 599, 600 iPSCs transplantation, 357 SIRT2 inhibitors, 600 MSC transplantation, 358 Sleep, 7 NSCs transplantation, 358, 359 Sleep apnea, 734, 735 Stenosis of intracranial arteries, 190 Index 855

Steroids Superoxide dismutase 1 (SOD1), 620, 627, 633 dehydroepiandrosterone (DHEA), 154 Survival in motor neuron (SMN), 391 peripheral glands, 154 Suspended animation and neuroprotection, 167 sulforaphane, 154 Synaptic activation, NMDA receptors, 600 Streptococcus pneumoniae, 703 Synaptic vesicle glycoprotein 2C (SV2C), 413 Stress-induced neuropsychiatric disorders Synaptopathies

A2AR antagonist, 741 advantages, 647 and dementia, 742 ASD, 647 neurotrophic factors, 741, 742 CNS, 647 Striatal neuron model, 600 concept, 647 Stroke FXS, 648 cerebral edema, 182 (see also gene mutations, 647 Cerebrovascular malformations) structure and function, 647 cyclophilin inhibitors, 682 Synergistic or antagonistic effects, 310 cytokines and adhesion molecules (see Systemic disorders Cytokines and adhesion molecules) cardiovascular disorders, 707–709 death cause after myocardial infarction, 179 diabetes, 709–712 extracellular glutamate, 182 fever, 715–718 focal neurological deficits, 178 liver disorders, 712–714 global cerebral ischemia/hypoxia, 179 renal disease, 714, 715 hemorrhage, types, 179 HSP, 183 intracerebral hemorrhage, 190 T ion channel dysfunction, 181 T cell receptors, 667 ischemic, 192 (see also Neurosurgical T cell-based personalized vaccine procedures) MS, 680 NTFs, 185, 186 (see also Pharmacologic Talampanel, 634 neuroprotective agents) Tamoxifen, 634 prevention of, 271 TAR DNA Binding Protein 43 (TDP-43), risk of, 189 291, 634 secondary prevention, 193 Targeted temperature management (TTM), 807 stenosis of intracranial arteries, 190 Targeting multiple pathways, 602 TIA, 192, 193 Tasquinimod, 410 treatment, 189 Tau, 470 See also Biological therapies Tauroursodeoxycholic acid (TUDCA), 155, Stroke vaccine, 229 198, 595 ST-segment elevation myocardial infarction Temporal correlation mapping (TCM) (STEMI), 708 technique, 35 Subarachnoid hemorrhage (SAH), 819 Temporal lobe epilepsy (TLE), 661–663 vasospasm, 819 Teriflunomide ADP-ribosylation, 821 MS, 696 DCI, 822 Testosterone drainage, CSF, 820 AD, 548 lumbar drainage, 820 Tetanus toxin, 155 pharmacological agents, 820 Tetrabenazine, 602 rhEPO, 820 Tetrahydrocannabinol tissue plasminogen activator, 822 AD, 529, 530 Triple-H approach, 822 Therapeutic antioxidants Subcortical vascular dementia, 653 alpha-phenyl-tert-butylnitrone, 78 therapeutic approaches, 653, 654 coenzyme Q10 (CoQ10), 79 Substantia nigra pars compacta (SNpc), 414, 415 dihydroergocryptine, 80 Sulindac, 789 flavonoids, 80 Superoxide dismutase (SOD), 615 mitochondria-targeted antioxidants, 81 radiation-induced hippocampal neuroleptic drugs, 81 dysfunction, 724 nitrones, 82 856 Index

Therapeutic antioxidants (cont.) topiramate, 324 NRF2, 82 types, 324 quercetin, 83 amantadine, 299 Therapeutic hypothermia (TH), 708 antioxidants, 299 Therapeutic radiation, CNS lesions barbiturates, 299 catalase reduces mitochondrial ROS, BCAAs, 310, 311 724, 725 beta blockers, 300 radiation encephalopathy, 723, 724 biological approaches (see Biological SOD, 724 approaches)

Thioredoxin, 782 BK B2 antagonists, 300, 301 Thrombectomy, 243 blood circulation, 313 Thrombolytic agents, 156 CDK inhibitors, 301 Thrombosis inhibitors, 229 cell therapy, 316, 317 Thyrotropin-releasing hormone (TRH), 146 classification, 283 Tissue plasminogen activator (tPA), 315 clinical trials (see Clinical trials) Tocopherols (TCTs), 231 cognitive abilities, 311 Tocotrienols, 203 COX-2 inhibitors, 301, 302 Tolerance-directed immunotherapy creatine dietary supplementation, 311 MS, 696, 697 cyclosporin, 302 Toll-like receptor 3 (TLR3), 795 dexanabinol, 302, 303 Toll-like receptors (TLRs), 348 DHA, 312 Topiramate, 324 epidemiology, 284 Toxic encephalopathies EPO, 303 alcohol vs. glutamate-induced excitotoxicity, 309 alcoholic neurologic disorders, 721 gold salts, 303 alcohol-induced damage, nervous HDACis, 304 system, 722 ISR, 304 FAS, 722 late sequelae, 323, 324 neurotoxicity, 722, 723 levosimendan, 304, 305 brain structures, 718 magnesium sulfate, 305 chemotherapy-induced brain damage, management (see Management) 720, 721 mechanisms/pathways, 285 organophosphorus poisoning, 719, 720 military, 284 Transcranial magnetic stimulation (TCM), 167 minocycline, 305, 306 Transcription factor (TF)-driven approach, 746 mitochondrial pathology, 315 Transcription factor Nrf2 activation, 13 mTOR, 314, 315 Transforming growth factor-β1 (TGF-β1), 124 multipotential neuroprotective Transgenic mouse models, 33 agents, 306 Transient ischemic attack (TIA), 192, 193 neuroprotective strategies, 285, 297 Transient receptor potential melastatin 4 neurosteroids, 307, 308 (TRPM4) cation channel nicotinamide, 311, 312 blockers, 673 NMDA receptors, 309 Transplantation of cells Nogo-A inhibitor, 309 BBB construction, NSCs, 86 non-pharmaceutical approaches glucocorticoids, 86 (see Non-pharmaceutical neuroprotective substances, 85 approaches) stem cells, 85 NTFs, 306, 307 Transverse myelitis (TM), 698, 699 nutritional approaches, 310 Trauma omega-3 fatty acid, 312 cerebral hypoxia/ischemia, 283, 284 oxygen carriers, 313 Traumatic brain injury (TBI), 773 pathophysiology (see Pathophysiology) and AD, 495, 496 PEG, 314 AEDs vs. prophylactic neuroprotection levetiracetam, 324 helmets, 322, 323 PTE, 324 physical exercise, 323 Index 857

propofol, 314 Vesicular monoamine transporter 2 rehabilitation phase (VMAT2), 406 (see Neuroregeneration) Vigabatrin, 660 simvastatin, 315 Viral gene transfer tPA, 316 APPsα, 519 Trk receptors, 128 Viral infections TrkA and TrkB receptor agonists, 125 avian influenza, 381, 382 Tumor necrosis factor-α (TNF-α), 184, 777 HIV-1, 380, 381 Tyrosine kinase inhibitor (TKI), 628 Vitamin B, 559 Vitamin E, 559, 636 AD, 531 U Vitamins UB-311 vaccine, 557 AD Unconventional biologicals, 159 folic acid, 559, 560 Uncoupling protein 2, 156 vitamin B, 559 Uric acid (UA), 203, 352 vitamin E, 559 B12, 157 brain development and functioning, 157 V D, 158 Vaccines, 157 VLA-4 (α4β1 integrin), 675, 680 AD Voltage-gated sodium channels, 672 active and passive immunotherapy, 558 Voltage-sensitive calcium channels (VSCCs), 816 active immunization with Aβ, 555, 556 Aβ immunization reduces Aβ plaque W pathology, 557, 558 Wallerian degeneration, 752 immunogenicity, 557 Wallerian degeneration slow (WldS) protein inflammatory profile, 558 PNS, 753 MAb, 556 Walter Reed Army Institute of Research MPL, 557 (WRAIR), 302 proinflammatory, 558 Whole brain radiation therapy (WBRT), UB-311, 557 723, 724 Valproate in Dementia (VALID), 549 Wogonin, 137 Valproic acid (VPA), 63, 359 AD, 549 Vascular dementia X characterization, 653 Xenon, 806, 807 definition, 652 prediction, risk factors, 653 subcortical, 653, 654 Y Vascular endothelial growth factor (VEGF), Yeast artificial chromosome (YAC128), 601 124, 635, 785, 795, 824 Vascular risk factors, 653 Vasoactive intestinal peptide (VIP), Z 146, 532 Ziconotide (Prialt), 111 Vasospasm, 819 Zinc, 493, 494