Neurobiology of Peripheral Nerve Regeneration Douglas W

Cambridge University Press 978-0-521-86717-7 - Neurobiology of Peripheral Nerve Regeneration Douglas W. Zochodne Index More information

Index

A alpha sensory axon 10, 17 adenomatous polyposis arteriovenous shunts A beta sensory axon 10, 18, 82 coli tumor suppressor (AV shunts) 13, 154 A delta sensory axon 10, 18, protein (APC) 87, anterograde neuron labeling 33, 35, 81, 142 102, 190 74, 74 A5E3 108 adhesive point contacts 210 apolipoprotein E A-60 19 adrenergic axons, terminals Arp 2/3 complex 87, 101, abaxonal Schwann cell 13, 155–157 209 cytoplasm 23 age, and impact on Artemin 191, 192–193 acetylcholine (Ach) 37 regeneration 215 autocrine support of acetylcholinesterase (AchE) agrin 146, 176 neurons 120 123 Akt (PKB; protein kinase B; autonomic nervous system acetylcholine receptors (AchR) V-akt murine thymoma 8, 31 69, 146 viral oncogene homolog) autonomic neurons 8, 31 ACTH (adrenal corticotrophic 87, 103–104, 120, autoregulation 13, 27, hormone) and 124, 128, 188–189, 156–157 regeneration 213 193–194, 211 axon direction finding, actin, F-actin, G-actin 19, 97, allodynia 55, 75–76, 141, guidance, misdirection 99, 101, 123–125, 209 143, 150 115–116, 143–145, 198 actin interacting protein alpha internexin 19, 21, 123 axon growth rate 94 87, 101 alpha motor neuron (axon) 10, axon sprouting 71, 91, 128, actin monomer binding 18, 25 135, 140 proteins 87, 101 alpha2-chimaerin 104 (see also Regenerative activating transcription factor AMPA receptor 29 sprouting) 3 (ATF3) 122–123, 193 amphoterin 127 axonal endbulbs activity, and impact on angiogenesis in peripheral (see Endbulbs, axonal) regeneration 218 nerves 106, 166 axonal protein synthesis acute motor and sensory ankyrin 19 124–126, 198

axonal neuropathy ankyrinG 25 axonal pruning 93, 128–129 (AMSAN) 2 anterior (gray matter) axolemma 19 adaxonal Schwann cell horn of the spinal axonotmesis 39–41, 43, 52 cytoplasm 23 cord 6, 8, 26 axoplasmic reticulum 19

267

268 Index

axoplasmic transport, Ca2þ-calmodulin-dependent chronic constriction injury anterograde, retrograde protein kinase I (CCI) 54–55, 143, 163 and slow 22, 91 (CaMKI) 105 Chung model of neuropathic axotomy 6, 119, 121, 151 calpain 46, 105 pain 33–34, 55 campenot compartmental ciliary neurotrophic factor Bands of Bungner 92, 106, 174 cultures 80, 198 (CNTF) 118, 176–177, basement membrane 22, cannabanoid receptor 29 190–191, 199, 202–203 112, 207 cap Z 101 cofilin 87, 101–102, 124 beam walking test 78 cardiotropin-1 (CT-1) 190–191 cold sensory testing 76, 150 beta-thymosin 125 casein kinase II (CK2) 103 collagen 11–12, 14–15, 22, blocking of neuromuscular caspase-3 124 147, 174, 211 junction transmission Caspr 25, 49–50 collapsin-response mediator 140 caveolin 119 proteins (CRMPs) 87, blood flow see nerve blood flow CDC 11, 34, 87, 99, 102, 155, 103–104 blood–ganglion barrier 27 190, 193 collateral sprouting of axons, blood–nerve barrier (BNB) celiac ganglia 8, 10, 31 collateral reinnervation 14–15, 57 cell adhesion molecules 76, 81–82, 128–130, 139, bone morphogenetic proteins (CAMs) 206–207 142, 150, 172, 180, 201 (BMPs) 191 cell body reaction to compartment syndrome 39, brachial plexus 10 axotomy 121–122 41, 55, 162, 166 bradykinin receptor 29 central chromatolysis 121 compliance 11 brain-derived neurotrophic central nervous system (CNS) compound muscle action factor (BDNF) 30, 98, plasticity in response potential (CMAP) 43, 100, 118, 123, 127, 144, to peripheral nerve 67–69, 138, 148, 146–148, 184–190, 191, lesions 150 163–164, 178 198–204 central nervous system (CNS), compression injuries to nerve regeneration of (see Entrapment nerve C unmyelinated axons 33, peripheral axons into 217 injuries) 81, 142 CNS topographical maps 151 conduction block 40, 42–43, cadherins 24, 207 (see also cervical and lumbar 164 (see also Ischemia, N-cadherin) enlargement 8, 10, 26 conduction block) calcitonin gene-related cervical ganglia 8 conduction velocity 66, 68, 138 peptide (CGRP) 13–14, Charcot–Marie–Tooth disease Connexin 32 (Cx32) 10, 18, 29–30, 32, 63, 66, 76, (CMT) 24–25 24, 25 88, 90, 94, 108, 141, 143, chemoreceptors 34 Contactin 25 155, 159, 166, 173, 179, cholesterol 91 contralateral effects of 211, 215 cholineacetyltransferase(ChAT) axotomy 122 þ calcium (Ca2 ) channels 29 11, 32, 37, 63, 123, 173 Cortactin 101 calcium-activated potassium cholinergic axons, cranial ganglia 8, 27 channel (KCa) 29 terminals 34 cyclic AMP (cAMP) 102, 108, calmodulin 105 chondroitin sulphate 126, 146, 189, 200, 213, Ca2þ-calmodulin-dependent proteoglycan (CSPG) 23, 217–218 protein kinase II (CaMK II) 50, 99, 102, 104, 175, 190, cyclic AMP phosphodiesterase 97, 128, 209, 211 200, 211–212, 217 126, 193

269Index

cyclic AMP response E-cadherin 24 epineurium, epineurial element-binding protein (see also Cadherins) sheath 10, 12 (CREB) 109, 189 E3/E4 ubiquitin ligases 46, 118 Erb neuregulin receptors 49, cyclin-dependent kinase ectopic discharges associated 118–119, 140, 174 (CDK) 104 with neuropathic pain erythropoietin (EPO) 51, cytoskeleton-associated protein- 88, 90 191, 194 23 (CAP-23) 105, 122 Edinger–Westphal nucleus 31 estrogen and regeneration 213 electrical silence of eukaryotic translation demyelination 39–40, 42–43 denervated muscles 177 initiation factor-4E dendritic arbours and electrical stimulation, impact (eIF-4E) 124 axotomy of motor on regeneration 144, evoked potentials 71 neurons 150–151 202, 219 explants of neurons for denervation, long-term of electrodecremental response regeneration studies nerve trunks 173–175 in testing neuromuscular 80, 183 denervation, long-term of junction 140 EXT2 (hereditary multiple nerve trunks, reasons 170 electromyography (EMG), exostoses gene) 123 desert hedgehog protein (Dhh) needle electromyography extracellular signal-related 51, 87, 131 69, 139–140, 178 protein kinases (ERKs) desert hedgehog protein electron microscopy (EM; thin 189, 192, 194, 197 receptors 131 sections for microscopy) ezrin 49–50 desiccation artifact of 18, 60, 83, 95, 106 nerve 59–60 Ena/Mena/VASP 101 F-spondin 145, 211 diabetes mellitus and endbulbs, axonal 52, 88–92 F waves 67, 70 regeneration 216 endoneurial blood flow fascicles 13, 15–16 diabetic neuropathy 130, compartment 155 fibrillation potentials 43, 69, 162, 165, 180 endoneurial capillaries 155 138–140, 178 diacylglycerol 189 endoneurium 14–16, 155 fibroblast 131 digestion chambers, axon endothelin (ET) 29, 163 fibroblast growth factors or myelin 48 endothelin receptor 29 (FGFs) 108, 118, 123, 149, dishevelled proteins 62, 103 endosomes 19 191, 193, 199–200, 203 dissector, physical or enkephalin 32, 88, 122 fibroblast growth factor optical for unbiased enteric nervous system 8, 10, receptor (FGFR) 29, 191, cell counts 119 31–32, 118 193, 203 dorsal horn of spinal cord 10 entrapment, or compression fibronectin 22, 116, 200, dorsal root entry zone nerve injuries 56, 67, 166 209–211 (DREZ) 217 ephrin 99 filopodia of growth cones 95 dorsal root ganglion (DRG) epidermal growth factor (EGF) fixation of nerves 61, 83 28–30, 56, 109, 157 191, 194 fixation artifacts of nerve dorsal root ganglion blood epidermal growth factor 60–61 flow 157 receptor (EGFR) 29, 99, 191 FK506-binding proteins dorsal root ganglion, ischemia epidermis 33, 71, 140–143 (FKBPs) 213 of 165 (see also Skin innervation) flexion contractures, paw from dynein 22, 98, 126 epineurialarterioles13,156 prolonged denervation dystroglycan 147 epineurial plexus 11, 155, 168 79, 149, 178–179

270 Index

fluorogold 72–73 Glypican-1 147 hydrogen clearance focalized proteolysis 212 GM1 ganglioside 29 polarography (HC) fodrin 19 Golgi organs 19, 86 158–160 forelimb testing of Golgi tendon organs 34–35 hypercarbia, impact on nerve reinnervation in rats gray rami communicans 31 blood flow 156 76, 150 grip strength testing 150 hyperemia of nerve blood forskolin and regeneration 213 growth-associated protein 43 flow 166 (GAP43/B50) 65, 87, 104, hyperpolarization-activated G ratio 23, 62 106, 108, 122–123, 143, cyclic-nucleotide gated Gp130 receptor subunit 173, 189, 214 (HCN) 29–30 190–191, 199 growth cone 79, 88, 90, 95–96, hypogastric ganglia 8, 10 galanin 29, 66, 88, 122 100, 107, 124–125 galanin receptor 29 growth cone organizing IB-4 (isolectin B-4) sensory galectin-1 127 complex (GCOC) 86 neuron subtype 11, 30, gamma motor axon 10, 18, growth hormone (GH) and 66, 142, 186, 192–193, 25, 34 regeneration 213 197, 211 ganglion blood flow 27 Guillain–Barre´ Syndrome image analysis of nerves, gangliosides and regeneration (GBS) 2–3, 130 ganglia 61 213 immunohistochemistry 11, gap, proximal to distal H waves, reflexes 70 66, 115 stump following nerve hair sensory receptors 32, immunophilins 213 transection 64, 133–134, 35, 142, 180 importin 126 201–203 hand reimplantation, importin-vimentin-pErk gap junctions (zona adherens) reinnervation following retrograde signal 126 14 141, 151 in vitro measures of glial-axon junction 24 handling artifact of regeneration 79 glial-derived neurotrophic histological samples 59 injury potentials after nerve factor (GDNF) 11, 30, 118, Hargreaves apparatus for damage 85 146, 148, 174, 186, thermal testing 75–76 inner mesaxon 23, 147 191–192, 197–204 heat shock protein 27 (HSP 27) innervation ratio 27 glial-derived neurotrophic 120, 122–124 inositol 1,4,5-triphosphate factor receptors 29, 123, heparan (heparin) sulphate (IP3) 189, 214 191, 192–193, 199 proteoglycan 116, 123, insulin 108, 118, 125, 191, glial fibrillary acidic protein 192–193, 211 194, 203, 216 (GFAP) 106, 109, 113, hepatocyte growth factor insulin-like growth factors 115, 145 (HGF) 146, 191, 195, 199 (IGFs) 108–109, 118, 146, glycogen synthase kinase 3b histamine 14, 179 176, 191, 194, 199–200, (GSK3b) 87, 102–104, 188, histamine receptor 29 202–204, 216 190, 209, 212 HNK-1 (human natural killer insulin-like growth factor glutamate receptors 29 leukocyte epitope; L2) receptors (IGF-R) glycogen depletion method to 144, 207 191, 194 study motor units 136 horizontal ladder test 79, 150 insulin receptors (IRs) 191, 194 glycolytic (Type II) muscle HuD (RNA binding protein) insulin receptor substrate fibers 36, 136 123 (IRS) 194–195

271Index

interferon-g (IFN-g) 50 lamina densa 22 microglia 119 integrins 103, 109, 116, lamina lucida 22 microtubules 19–20, 21–86, 119, 142, 147, 207, laminin 22, 50, 103, 116, 95–96, 98 209–211 147, 192, 208–211 microtubule associated interleukins 50, 87, 109, 118, laser doppler flowmetry (LDF) (binding) proteins 123, 127, 190–191, 158, 159–160, 161 (MAPs or MBPs) 22, 98 198–199, 203 leukemia inhibitory microsphere embolization to intermediate early genes 122 factor (LIF) 51, 109, measure nerve blood flow intermediate filament 19 118, 123, 127, 190–191, 158, 161 internodes 16, 25, 40 199 miniature endplate potentials intraperiod line 23, 147 LIM kinase 87, 101 (MEPPs) 37 iodoantipyrene [C14] LINGO 99 minifascicles 15, 54, 61–62, autoradiography or lipoprotein receptor-related 114–115, 130, 134, distribution 158, 161 protein (LRP-1) 109, 195 168, 176 ischemia of ganglia (see dorsal lumbosacral plexus 10 mitochondria 19–20 rootganglion,ischemiaof ) lymphatic vessels in the mitogen-activated protein ischemia of nerve 11, 153, peripheral nerve trunk kinase (MAPK) 102, 162–165 12, 14, 193 118, 122, 128, 189, ischemia of nerve during lysosomes 19 193, 195, 211, 214 injury 165, 168 mixed spinal nerve 10 ischemia, centrofascicular of macrophages 45, 48, 50, 52, monocyte chemoattractant nerve 153 86, 127 protein-1 (MCP-1) ischemia, nerve conduction macrophage inflammatory 50, 109 block 163–164 protein 1a (MIP 1a) 50 mononeuritis multiplex 162 (see also resistance to macrophage stimulating mononeuropathy 1 ischemic conduction protein (MSP) 191, 195 morphological measures failure) major dense line 23, 147 of nerve blood vessels 161 mast cells 14, 16, 52, 76, motor neurons 6, 8, 10, 25–26, JAK (janus-kinase) and STAT 106, 131, 179, 198 150 (signal transducer and matrix metalloproteinases motor recovery 77–79, 149 activator of transcription) (MMPs) 50, 175, 212 motor unit 26, 70, 129, 136, pathway 190 mDia 99 177 (see also voluntary Jitter indicating unstable mechanical sensitivity, motor unit potentials) neuromuscular hyperalgesia 75–76, motor units, giant 139–140, transmission 139–140 141, 150 177 juxtaparanode 24–25 Meissner’s corpuscles (FAI) motor unit force 33, 35, 142–143, 180 measurements 70, 138 kainate receptor 29 mesenteric ganglia 8, 10, 31 motorunitnumberestimation katanin 87, 98 Merkel touch complexes, (MUNE) 69, 138 kinesin 22, 98 domes (SAI) 32, 35, multifiber nerve conduction Krox20 (Egr2) 147 142, 180 recordings 66 metabosensitive afferent muscle ATPase stain for L1 118, 142, 207 axons 77 fiber types 136 lamellipodia 95 microfilaments 19 muscle atrophy 138, 177

272 Index

muscle denervation 43, 69, nerve blood flow after neuropoietic cytokines 118 175–178, 179 injury 166 neurotmesis 39, 41–43, muscle fiber type grouping nerve and ganglion blood flow 51–52, 172 136 measurement methods neurotrophic hypothesis 119, muscle grouped fiber 158–161 186–187, 196 atrophy 137 nerve growth factor (NGF) neurotrophin-3 (NT-3) 30, muscle reinnervation 135 80, 98, 100, 103, 118, 109, 123, 145–146, muscle specific kinase 125, 128, 146–147, 184–190, 191, 198–204, (MuSK) 37 182–183, 191, 197–204, 209 muscle spindles 34, 185 212, 214 neurotrophin-4/5 (NT-4/5) mTOR (see target (mammalian) nervi nervorum 14 123, 146, 184, 191, of rapamycin) nestin 145 198–204 myelin 23–24, 24 Nests of Nageotte 119 neurotrophin-6 (NT-6) 184 myelin and lymphocyte Netrin 100, 128 neurotrophin-7 (NT-7) 184 protein (MAL) 24 neural cell adhesion molecule neurotrophins, neurotrophic myelin associated (NCAM,Nr-CAM) 25, growth factors 30, glycoprotein (MAG) 108, 118, 144, 174–175, 118, 182, 184–185, 24–25, 99, 102, 192, 207 191, 196–204 200, 207 neurapraxia 39–40, 42, 171 neurovascular bundle 11 myelin basic protein (MBP) neuregulins (NRGs) 49, 87, neurturin 191, 192–193 24, 63 108, 119, 137, 147, Nexin-1 213 myelin ovoids 44 175–177, 194 nicotinamide myelination, remyelination neurites, in vitro neuron mononucleotide 23, 148 cultures 79, 91 adenylyltransferase myelinated axon 10, 16–17, neuroeffector junction 32 (NMNAT) 47 20, 60 neurofascin 24–25 Nissl substance 27, 121 myelinated fiber density neurofilament 19–20, 20–21, nitric oxide (NO) 51, 89, 155, 18, 61 29, 36, 46, 65, 73, 86, 166, 194 myenteric (Auerbach’s) 88, 90, 106–107, 115–117, nitric oxide synthases (NOS) plexus 32 121–122, 208 51, 88, 122 myosin in growth cones 99 neurogenic inflammation nociceptin 29, 66, 88, 122 myristoylated alanine-rich 76, 179 nociception 33 protein kinase C neurokinin receptor (NK1) 29 nociceptive 11, 18, 35, 201 substrate (MARCKS) 105 neuroma 51–52, 168, 173, 176 nociceptors 33, 35 neuroma “in continuity” nodes of Ranvier 16–17, 20, N-cadherin 118, 174–175 52–54, 175 23–24, 25, 128 N-WASP 101 neuromuscular junction 36, Nogo 24, 99, 212 Nancy B 2 71, 104, 135, 138–139, 146 Nogo receptor (NgR) 99, Necdin 188 neuropathic pain 4, 54 128 Neotrofin 204 neuropathy 1, 3–4, 12 nuclear localization signal nerve action potentials (NAPs) neuropeptide Y 32, 88, 122 (NLS) 126 66, 163 neuropilin receptors for nuclear magnetic resonance nerve blood flow 12, 153–169, semaphorins (NP-1 and spectroscopy (NMRS) of 159–160, 169 NP-2) 104, 214 muscle 178

273Index

nuclear transcription factor paranode–node–paranode phosphatidylinositol kappa B (NFkB) 87, 102, (PNP) 24 3,4,5-triphosphate (PIP3; 127, 188, 194 paraspinal sympathetic PI(3)P) 103–105, 188

ganglia 8, 10, 31 phospholipase A2 (PLA2) 214 Oct6 (SCIP/TstI) 147 parasympathetic axons 31 phospholipase C g (PLC-g) oligodendrocyte myelin parathyroid hormone-related 188–189, 192, 195, 214 glycoprotein 99 peptide (PTHrP) 109 pilomotor axons 34 oncomodulin 127–128 pelvic splanchnic nerves 31 pinch test of regeneration 74 oncostatin 118, 190–191 peptidergic axons, terminals pincher pinocytotic protein opioid receptors 29, 88 13, 155 197–198 opioid-like receptor 1, 3–4, periaxin 24 pinocytotic vesicles 14 12, 29 periaxonal space 23 pioneer axons 94 outer mesaxon 23, 147 pericytes 15 pituitary adenylate oxidative (Type I) muscle perikarya 8 cyclase-activating fibers 36, 136 perineurium 14, 131 polypeptide (PACAP) oxygen tensions, endoneurial perineuronal satellite (glial) 29, 190 157, 161 cell 6, 27–28, 108–109, plasma extravasation 76 119, 124, 145 platelet-derived growth factor p21-activated kinase (PAK) peripheral myelin protein 22 (PDGF) 108–109, 191, 87, 102 (PMP 22) 24 194, 204 P31 NMR spectroscopy of peripheral nerve trunk 4, 8, 10 pleiotrophin 146, 190–191, muscle, and peripherin 19, 21, 123–124 195, 199, 204 denervation 178 peroxynitrite 51 poly ADP-ribose polymerase p38 124 Perroncito, structures of 88 (PARP) 189 p53 tumor suppressor persephin 191, 192–193 polyamines and regeneration family 120 PGP 9.5 (Protein gene 217 p75 growth factor product 9.5) ubiquitin polyneuronal innervation of receptor 29–30, 98, hydrolase axon label 33, muscles 135 103, 106, 122, 142, 174, 65, 71, 81, 106–107, 115, polyneuropathy 1 184, 190–191, 199, 141, 143 polyribosomes 19 202–204 phantom sensations 151 polysialic acid moiety of pErk 126 phosphatase and tensin NCAM 144, 207 P0 protein (MPZ) 24, 147, 207 homolog deleted on position sensibility 35 P2 protein 24 chromosome ten (PTEN) (see also proprioception) Pacinian corpuscles 33, 35, 87, 103–104, 188 positive sharp waves 43, 69 142, 180 phosphatidylcholine 91 posterior columns of spinal pancreatitis-associated phosphatidylinositol-3-kinase cord 10 þ protein III (PAP-III) 51 (PI3K; PI3-kinase) 97, potassium (K )channels25, 29 para-aortic ganglia 8, 10 103, 118, 120, 124, 128, precapillary sphincters 13 paracrine support of 188–190, 192–195, 209, preconditioning neurons 120 211–212, 214 (conditioning) 124, 218 paraesthesiae 141 phosphatidylinositol preferential motor paranodal bulbs 23 4,5-bis-phosphate (PIP2; PI reinnervation (PMR) 129, paranode 23–25 (2)P) 87, 101, 103, 105, 188 144–145, 219

274 Index

presynaptic Schwann cells 36 Remak bundle 17–18, Scar/WAVE 101 pro-NGF (pro-nerve growth 22–23, 108 Schwann cell 6, 16, 22–23, 107 factor) 186–187, 188 Renaut bodies 19 (see also Reactive Schwann profilin 87, 101 repetitive nerve stimulation cells) proneurotrophin 99 technique to assess Schwann cell, terminal or proprioception 4, 142 neuromuscular junctions perisynaptic (see terminal (see also position 138–139 Schwann cells) sensibility) reperfusion injuries of sciatic functional index (SFI) protudin 91 peripheral nerves 162 77–78 protein kinase A (PKA) 200 repulsive guidance molecule Schmidt–Laterman clefts or protein kinase C (PKC) (RGM) 215 incisures 23, 147 104–105, 118, 120, resistance to ischemic Seddon classification of 122, 189 conduction failure nerve injuries 39, 41, pseudonerves 110 (RICF) 163 55, 162, 166 purinergic receptor 29–30, 197 retrograde degeneration of segmental demyelination 40 neurons and axons 86, Semaphorin 87, 99, 102, RabGTPase 197 119–120, 172 104, 131, 200, 211, 214 RAC 87, 99–100, 102, 104, (see also traumatic Semithin plastic (epon) light 190, 192, 211 degeneration) microscopy tissue Ran-2 108 retrograde labeling of sections 13, 26, 28, 58–59, Rapsyn 37 neurons 72–73 83, 114, 134 Ras superfamily GTPases 99, Rexed lamina 25 sensory nerve action potentials 102, 188–189, 192–193, RHO family GTPases 97, (SNAPs) 66, 141, 149 195, 214 (see also RHO 100, 102, 188, 190, sensory neuron 8, 10, 27–30, family GTPases) 209–212 96, 111–112 reactive Schwann cells 81, RHO kinase (ROK) 87, 99, sensory recovery 75–77, 149 106–107, 111, 113, 174 102, 211–212 serotonin 14 receptor for advanced RHOA 87, 99–100, 102, 104, Sholl analysis of neurite glycosylation 125, 211 outgrowth 80 endproducts (RAGE) ribosomal periaxoplasmic single fiber electromyography 51, 127 plaque domains 22 (SFEMG) 139–140 regeneration associated genes ribosomal-P0 124 SIRT1 (Silent information (RAGs) 120, 122, 125, 172, root avulsion 120 regulator mammalian 196, 218 Ruffini endbulbs (SAII) 32, 35 protein; sirtuin) 47 regeneration conduit 64, skin denervation 179 114–116, 133–134, 149, S-100 immunohistochemical skin innervation 32–33, 71, 200, 202 marker of Schwann 140–143 regeneration rate of cells 81 skin ulceration 179 axons 170 safety factor for (see also Wound healing, regeneration units 95, 112 neuromuscular skin) regenerative sprouting 45, 89, transmission 138, 140 slingshot 87, 101 92–94, 116, 128 saltatory transmission 16 sodium (Naþ) channels 25, (see also Axon sprouting) satellite cells 6, 27–28, 29, 88 Reich granules 22 108–109, 119, 124, 145 somatostatin 29, 32

275Index

somatostatin receptor 29 target (mammalian) of tubulin 21, 63, 65, 80, 98, Sox10 (Sry-related HMG rapamycin (TOR; mTOR) 106, 110, 115, 117, box 10) 147 124, 128 122–123, 210 spectrin 25 tenascin 116, 211 tumor necrosis factor-a sphenopalatine ganglion 31 tensile properties 11 (TNF-a) 50, 109, 127 spinal ganglia 27 terminal (perisynaptic) tyrosine hydroxylase (Th) spondylosis 165, 171 Schwann cells 104, 11, 32 staggered axonal regrowth 135, 142, 177, 180, 218 93–95, 171 testosterone and ubiquitin 124 staircase test 79, 150 regeneration 213 ubiquitin-proteasome STAT3 (Signal Transducer thermal sensation, system (UPS) 47 and Activator of hyperalgesia 18, 33, 75, uncoupling protein 3 (UCP3) Transcription 3) 127 141, 143, 149–150 195 stem cells, peripheral thyroxine (thyroid unmyelinated axon 10–11, neuronal 145 hormone) and 18–19 stretch injuries 56 regeneration 213 unmyelinated fiber density substance P (SP) 11, 13, 29, tight junctions (zona 19, 60 62–63, 76, 88, 143, 155, occludens) 14–15 159, 179, 185 tissue plasminogen activator vasa nervoum 11, 15–16, submandibular ganglion 31 (tPA) 213 153–154, 167, 169 submucous (Meissner’s) transforming growth vascular endothelial plexus 32 factor-b (TGF-b) 50, 148, growth factor (VEGF) Suc1-associated neurotrophic 191, 193, 204 146, 166, 175, 191, factor-induced tyrosine transient receptor potential 195, 199 phosphorylated target proteins (TRPs) 29, 34 vasculitic neuropathy 4 (SNT) 188 transitional zone (TZ) 19 vasoactive intestinal Sunderland classification of traumatic degeneration 46–47 polypeptide (VIP) nerve injuries 42 (see also retrograde 29, 32, 141, 143, superior cervical ganglia degeneration) 215 neural-specific 10 protein transient axonal glycoprotein- vasoconstriction 13–14, (SCG10) 122 1 (TAG-1; axononin-1) 24 155–157, 180 suppressor of cytokine triple response of Lewis 179 vasodilatation 13–14, 76, signaling (SOCS3) 190 tropomyosin 101, 124 155, 166 sweat glands 34, 71, 129, tropomyosin-related vesicle associated 143, 179 kinase A (Trk A) 29–30, membrane protein-1 sympathetic axons 11, 34, 98, 122, 147, 184–190, (VAMP-1) 123 155, 193 197, 202 vimentin 126 sympathetic ganglia 31 tropomyosin-related voluntary motor unit synaptophysin 106 kinase B (Trk B) 30, 98, potentials 69 123, 144, 184–190, 191, (see also Motor units) TAJ/TROY (toxicity and JNK 197, 202 voltage gated calcium inducer; member of tropomyosin-related kinase channels 36 the TNF receptor C (Trk C) 29–30, 98, voltage gated potassium superfamily) 99 122–123, 184–190, 191 channels 36

276 Index

von Frey hairs for 65, 86, 93, 118, 154, wrong way axons 116, 143 mechanical sensitivity 164, 173 testing 141, 150 walking track analysis 77–78, YFP thy-1 transgenic mice 149–150 66, 93, 203 Wallerian degeneration and watershed zones 11, 153 Wallerian-like White rami communicans 31 ZAS3 (Zinc finger protein, degeneration 5, 40–43, Wlds mouse mutant 47 acidic region, Ser/Thr 44–46, 48, 57, 62–63, wound healing, skin 179 rich) 87, 127