International Journal of Pharmacy Teaching & Practices 2015, Vol.6, Issue 4, 2620-2629. Role of Reactive Oxygen Species (ROS) and Cytokines i n Vascular Dementia: A Review Sunil Bansal1, Shamsher Singh* 1, Amit Sharma2 1.Department of Pharmacology, I.S.F College of Pharmacy, Moga, Punjab 2.Depatment of Pharmacy Practice, I.S.F College of Pharmacy, Moga, PunjaB Review Article various symptoms that occur due to 1 1 2 excessive neuronal damage By specific Please cite this paper as Sunil Bansal , Shamsher Singh* , Amit Sharma . Role of Reactive Oxygen Species (ROS) and Cytokines in Vascular Dementia: A diseases. These diseases include A Review. IJPTP, 2015, 6(4), 2620-2629. Alzheimer's disease and vascular dementia. Corresponding Author: Someone with dementia may experience Mr. Shamsher Singh loss of memory, mood changes, and M. Pharm. Assistant Professor proBlems with language [1, 2]. To be Department of Pharmacology, healthy and function properly, Brain cells I.S.F. College of Pharmacy, Moga need a good supply of Blood. Blood is Panjab, India -142001 delivered through a network of Blood E -mail: [email protected] vessels called the vascular system. If the Abstract vascular system within the Brain becomes damaged and Blood cannot reach the Brain Vascular dementia (VaD) causes impairment of memory and cells, the cells will eventually die [4]. This cognitive functioning due to reduction in the Blood flow and can lead to the onset of vascular dementia. oxygen supply to the brain. Vascular dementia is the second most common type of dementia after Alzheimer's disease. Given the importance of small vessel When the Blood supply to the Brain is interrupted, Brain cells disease in vascular dementia and vascular are deprived of vital oxygen and nutrients, causing damage to cognitive impairment, it is reasonable to the cortex of the Brain - the area associated with learning, suggest that cognitive dysfunction results at memory, and language. Vascular disease affects multiple cell least in part from interruption of axonal types within the neurovascular unit (NVU), including brain vascular cells (endothelial cells, pericytes, and vascular smooth connections Between one part of the muscle cells), glial cells (astrocytes and microglia), with rise in cereBral cortex and another, and Between inflammatory mediators (TNF-α, NF-kB, ROS, MAPK, TGF-β, IL- the cereBral cortex and deep grey matter 1, IL-6 and cytokines. GloBally in different population the [6, 7]. Small vessel disease affects causes of dementia may Be mixed. Vascular dementia arises as particularly frontal loBe white matter and a consequence of ischemic insults such as hemorrhage and hypoperfusion that trigger neurodegeneration. The the closely related Basal ganglia, so it is not deprivation of nerve cells from oxygen and glucose results in surprising that the cognitive dysfunction depletion of nerve cell structural integrities responsible for commonly seen in vascular dementia VaD. There are numBer of evidences which causes neuronal involves executive activity which is known loss like excitotoxicity through over calcium influx By NMDA to Be a function of the frontal loBe [9]. receptor, increase ROS level produces symptoms of VaD. CereBral amyloid angiopathy may also Keywords: Vascular dementia (VaD), vascular cognitive affect white matter function Because this is impairment, Cytokines the final destination for the Blood flowing in the cortical arterioles affected By this Introduction condition. In macro infarction, lacunas and Vascular dementia is CNS disorders, which micro infarction, it is the loss of neurons consequently cause cognitive impairment that is thought to Be important and there is (dementia) attriButable to cereBrovascular evidence that after a stroke, dementia is pathology. The term 'dementia' is descriBed to 2620 International Journal of Pharmacy Teaching & Practices 2015, Vol.6, Issue 4, 2620-2629. more likely if the stroke was severe, therefore predominant. Oxidative stress reflects an destroying more neurons [5]. This cereBral ischemia imBalance Between the systemic are energy failure occurs due to suBsequent events manifestation of reactive oxygen species including inflammation, glutamate-mediated and a Biological system's ability to readily excitotoxicity, calcium overload, initiation of detoxify the reactive intermediates [45]. ·− intracellular death pathways, oxidative stress Key anti-oxidants include O2 dismutases produces structural and functional changes occur. (SOD), glutathione peroxidases, and Mediators of these events interact with each other catalase. ROS can Be generated By multiple and contriBute to cellular damage, in which a enzymes within the vasculature as well as ·− cholinergic deficit is involved, and finally cause non-enzymatic sources. O2 anion is the cognitive impairment or dementia [13]. There are parent ROS molecule produced By the one different types of vascular dementia stroke related electron reduction of molecular oxygen By dementia, suB cortical vascular dementia, mixed various oxidases (e.g., NADPH oxidase, dementia. Many of the factors that increase the risk cyclooxygenase, enzymes in the of vascular dementia are the same as those that mitochondrial electron transport chain, increase the risk of cardiovascular disease (like lipoxygenases, cytochrome P450 enzymes). ·− smoking). a medical history of stroke, high Blood O2 can then Be dismutase By SOD, pressure, high cholesterol, diabetes (particularly resulting in the generation of hydrogen type II), heart proBlems or sleep apnea, a lack of peroxide. DisturBances in the normal redox physical activity [4, 5]. Always consult a doctor if state of cells can cause toxic effects through you experience any sudden symptoms, such as the production of peroxides and free slurred speech, weakness on one side of the Body or radicals that damage all components of the Blurred vision even if they are only temporary. cell, including proteins, lipids, and DNA [41, These symptoms may Be caused By temporary 43]. The increase the level of reactive interruptions in the Blood supply within the Brain. oxygen species is responsible for Treatments are available But the vascular dementia suppresses apoptosis and promotes progresses vary from person to person. Although proliferation, invasiveness and metastasis. the Brain damage that causes vascular dementia An increased level of reactive oxygen cannot Be reversed, it may Be possiBle to slow the species in the vasculature, reduced nitric progression of the disease in a numBer of ways [10, oxide Bioavailability, and endothelial 11]. These are numBer of medications used treat dysfunction leading to vascular disease is any underlying conditions, such as stroke, high associated with vascular dementia. Blood pressure, high cholesterol, diabetes or heart Elevated reactive oxygen species proBlems adopting a healthier lifestyle By stopping production causes neuronal cell death and smoking, taking regular exercise, eating healthily to damage [41, 43]. Oxidative stress reduced regain their lost functions [14]. The FDA has issued the nitric oxide and increase Amyloid-Beta& guidelines on drug treatments for Alzheimer’s ApoE4.These oxidative stress include in disease (including cholinesterase inhiBitors and increase the reactive oxygen species memantine), But has not recommended these same Because effecting By aging and drugs for treating vascular dementia. These drugs homocystein. Proteasome inhiBition cause may, however, Be prescriBed to treat mixed neuronal dysfunction and neuronal death dementia, particularly when Alzheimer’s disease is can produce a vascular dementia [41, 42]. predominant [16]. When the Blood supply to the Brain is 2. Pathophysiological role of inflammatory reduced By a Blocked or diseased vascular mediator in vascular dementia system, vascular dementia occurs and leads 1. Role of Stress in vascular dementia to a progressive decline in memory and Vascular dementia are the most common types of cognitive function [29]. Chronic cereBral dementia with the former Being the most hypoperfusion can Be induced By 2621 International Journal of Pharmacy Teaching & Practices 2015, Vol.6, Issue 4, 2620-2629. permanent Bilateral common carotid artery occlusion in rats, resulting in significant white matter lesions, learning and memory impairment and hippocampal neuronal damage are cause vascular dementia [30]. 3. Role of cytokins and other inflammatory factors Vascular dementia characterized By severe neurodegenerative changes, such as cereBral atrophy, loss of neurons and synapses [41]. The Central Nervous System (CNS) has its own resident immune system, in which glial cells serve as a supportive and nutritive role for neurons [69]. The Fig1. Role of oxidative stress in vascular dementia evidence inferred a close association of neuroinflammation with the pathogenesis of several degenerative neurologic disorders, including AD [30]. Reactive 2. Effects of angiotensin II on the cerebral astrocytes can contain suBstantial amounts circulation: role of oxidative stress of different forms of amyloid Beta, Angiotensin II (Ang II) promotes oxidative stress in including amyloid Beta 1-42 (Aβ42) as well the vasculature via stimulation of AT1 receptors and as truncated forms (38, 39). Reactive suBsequent activation of NADPH oxidases. Oxidative astrocytes can take up and degrade stress contriButes to Blood-Brain Barrier (BBB) extracellular deposits of Aβ42 fig.3 and that dysfunction, impairment of vasodilation and this function is attenuated in ApoE-/- neurovascular