Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive oxygen species (ROS) accumulation has been described in the brain following an ischemic insult. Superoxide anion is converted by superoxide dismutase into hydrogen peroxide (H2O2), and the latter is then transformed into the toxic hydroxyl radical, through the Haber-Weiss reaction, converted to water by glutathione peroxidase (GPx) or dismuted to water and oxygen through catalase. Accumulation of H2O2 has been suggested to exert neurotoxic effects, although recent in vitro studies have demonstrated either physiological or protective roles of this molecule in the brain. In particular, oxidative stress is critically involved in brain damage induced by transient cerebral ischemia. Here, we demonstrate that inhibition of GPx by systemic (i.p.) administration of mercaptosuccinate (MS, 1.5-150 mg/kg) dose-dependently reduces brain infarct damage produced by transient (2 h) middle cerebral artery occlusion (MCAo) in rat. Neuroprotection was observed when the drug was administered 15 min before the ischemic insult, whereas no effect was detected when the drug was injected 1h before MCAo or upon reperfusion. Furthermore, application of MS (1 mM) to corticostriatal slices limited the irreversible functional derangement of field potentials caused by a prolonged (12 min) oxygen-glucose deprivation. This effect was reverted by concomitant bath application of the catalase inhibitor 3-aminotriazole (20mM), suggesting the involvement of catalase in mediating the neuroprotective effects of MS. Thus, our findings demonstrate that MS is neuroprotective in both in vivo and in vitro ischemic conditions, through a mechanism which may involve increased endogenous levels of H2O2 and its consequent conversion to molecular oxygen by catalase.
 ...
PMID:Oxidative stress in stroke pathophysiology validation of hydrogen peroxide metabolism as a pharmacological target to afford neuroprotection. 1960 81

Free radical induced neural damage is implicated in cerebral ischemia-reperfusion (IR) injury and antioxidants are reported to have neuroprotective activity. The present study was designed to assess the neuroprotective role of rutin (Vitamin P), and mechanism of action. The middle cerebral artery (MCA) of an adult male Wistar rat was occluded for 2 h and reperfused for 22 h. The administration of rutin (25 mg/kg bwt., orally) once daily for 21 days before middle cerebral artery occlusion (MCAO) showed marked reduction in infarct size, reduced the neurological deficits in terms of behaviors, suppressed neuronal loss and diminished the p53 expression in MCAO rats. A significantly depleted activity of antioxidant enzymes, glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD) and content of glutathione (GSH) in MCAO group were protected significantly in MCAO group pretreated with rutin. Conversely, the elevated level of thiobarbituric acid reactive species (TBARS), H(2)O(2) and protein carbonyl (PC) in MCAO group was attenuated significantly in rutin-pretreated group when compared with MCAO group. These results indicate that rutin attenuates ischemic neural apoptosis by reducing the expression of p53, preventing morphological changes and increasing endogenous antioxidant enzymatic activities. Thus, rutin treatment may represent a novel approach in lowering the risk or improving the function of ischemia-reperfusion brain injury-related disorders.
 ...
PMID:Rutin protects the neural damage induced by transient focal ischemia in rats. 1963 Nov 95

Ischemia/reperfusion injury ends up in the cascade of excitotoxic stimulation of superoxide and nitric oxide formation leading to the generation of highly reactive products, including peroxinitrite and hydroxyl radical, which are capable of damaging lipids, proteins and DNA. Several polyphenolic compounds scavenge the radicals and protect from injury. 5,7,3',4',5'-pentahydroxy dihdroflavanol-3-O-(2''-O-galloyl)-beta-d-glucopyranoside (AP1), a polyphenolic compound, isolated from Anogeissus pendula Edgew was tested for its neuroprotective effect in transient focal cerebral ischemia in rats. Transient focal cerebral ischemia was produced by middle cerebral artery occlusion for 2h for studying infarct volume, brain edema, apoptosis and oxidative stress. AP1 was tested for in vitro protection from glutamate and hydrogen peroxide-induced damage to Neuro-2a cells by MTT assay. It was also tested for its in vitro antioxidant, lipid peroxidation inhibition, NO scavenging and cyclooxygenase inhibitory activities. AP1 treatment (30 mg/kg i.p.) before reperfusion injury (0 h) significantly reduced the infarct volume, cerebral edema, number of apoptotic cells in penumbra and neurobehavioural abnormality score and lipid peroxidation, protein carbonyl levels and total thiols in brain. Increased catalase activity and NOx levels in ischemic animals were significantly reduced by AP1 treatment. AP1 (3 microg/ml) protected Neuro-2a cells to H2O2 and glutamate-induced damage. In in vitro studies, AP1 was found to possess reducing and NO scavenging activities. It also reduced lipid peroxidation and inhibited cyclooxygenase activity (cyclooxygenase-1 and cyclooxygenase-2). AP1 can be used as a neuroprotective agent in stroke as it reduced apoptosis and found to be a good antioxidant and anti-inflammatory compound.
 ...
PMID:Neuroprotective effect of 5,7,3',4',5'-pentahydroxy dihydroflavanol-3-O-(2''-O-galloyl)-beta-D-glucopyranoside, a polyphenolic compound in focal cerebral ischemia in rat. 1978 80

Stroke is a leading cause of adult disability and mortality. Diabetes is a major risk factor for stroke. Patients with diabetes have a higher incidence of stroke and a poorer prognosis after stroke. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a ligand-modulated transcriptional factor and a therapeutic target for treating type II diabetes. It is well-documented that activation of PPAR-gamma can also attenuate postischemic inflammation and damage. In this review, we focus on the newly revealed anti-apoptotic actions of PPAR-gamma against cerebral ischemia. PPAR-gamma, by increasing superoxide dismutase/catalase and decreasing nicotinamide adenine dinucleotide phosphate oxidase levels, attenuated ischemia-induced reactive oxygen species and subsequently alleviated the postischemic degradation of Bcl-2, Bcl-xl, and Akt. The preserved Akt phosphorylated Bad. Meanwhile, PPAR-gamma also promotes the transcription of 14-3-3epsilon. Elevated 14-3-3epsilon binds and sequesters p-Bad and prevents Bad translocation to neutralize the anti-apoptotic function of Bcl-2. This review further supports the notion that PPAR-gamma may serve as a potential therapeutic target for treating ischemic stroke.
 ...
PMID:Anti-apoptotic actions of PPAR-gamma against ischemic stroke. 2012 24

Increased attention has been paid to the role of oxidant/antioxidant imbalance in neurodegenerative process and pharmaceutical neuroprotective interventions. Food-derived compound luteolin possesses multitarget actions including reactive oxygen species (ROS)-scavenging activity in cultured human endothelial cells or permanent immature rat oligodendrocytes. This study aims to elucidate whether luteolin has a neuroprotective tendency toward ROS-insulted neural cells. The present results showed that luteolin, isolated from the ripe seed of Perilla frutescens (L.) Britt., markedly reversed hydrogen peroxide-induced cytotoxicity in primary culture cortical neurons but not in cultured human neuroblastoma cells. Upon the ROS-insulted primary neurons, luteolin concentration-dependently enhanced neuronal cell survival with efficacy higher than and potency similar to vitamin E. Additionally, luteolin significantly attenuated the increase in ROS production and prevented the decreases in activities of mitochondria, catalase, and glutathione in ROS-insulted primary neurons. Thus, luteolin functions by neuroprotection possibly through a rebalancing of pro-oxidant-antioxidant status. This agent points to possible interventions for preventing neurodegenerative diseases such as cerebral ischemia, Parkinson's disease, and Alzheimer's disease, as well as for improving brain aging.
 ...
PMID:Luteolin from Purple Perilla mitigates ROS insult particularly in primary neurons. 2038 51

The present study was designed to test pretreatment multiple doses of irbesartan (IRB) 50 mg, aspirin (ASP) 100 mg and the combination of both drugs for 7 days on middle cerebral artery-occluded (MCAO) rats. Focal cerebral ischemia was induced by MCA occlusion for 2 hours followed by reperfusion for 22 hours. After 24 hours of ischemia, grip strength and locomotor activity tests were performed. Animals were immediately sacrificed, infarct volume was measured followed by the estimation of markers of oxidative stress in the whole brains. Locomotor activity and grip strength were improved in IRB- and ASP-treated rats. Infarct volume was reduced in both IRB and ASP pretreatment as compared with MCAO rats. An elevation of thiobarbituric acid reactive substance (TBARS) and a reduction in glutathione (GSH) and antioxidant enzymes viz. superoxide dismutase (SOD) and catalase were observed following MCAO. Pretreatment of IRB and ASP showed the reduction in TBARS, elevation in GSH, SOD and catalase levels as compared with MCAO rats. The protective effects of IRB, an angiotensin II receptor antagonist having affinity for AT(1) receptor subtypes, could be due to inhibition of AT( 1) receptor expression in addition to its neuroprotective and free radical scavenging properties in cerebral ischemia. Further, it may be possible that the combination of IRB and ASP may be useful as an add-on therapy and would yield beneficial effects, if administered immediately following the ischemia in reducing the severity of the neurological deficits. However, our results are preliminary, further studies with posttreatment of IRB and ASP are required to provide more firm view.
 ...
PMID:Protective effect of irbesartan, an angiotensin II receptor antagonist, alone and in combination with aspirin on middle cerebral artery occlusion model of focal cerebral ischemia in rats. 2048 39

The aim of our study was to investigate the neuroprotective properties of shikonin, a naphthoquinone pigment isolated from the roots of the traditional Chinese herb Lithospermum erythrorhizon. In the present study, mice were divided randomly into sham, model, shikonin and edaravone-treated groups. Shikonin (50, 25, and 12.5mg/kg, i.g.) or maize oil was administered three times before ischemia and once at 2h after the onset of ischemia. Mice were anesthetized with chloral hydrate and subjected to middle cerebral artery 2h of occlusion and then 22h of reperfusion. Different antioxidant assays were employed in order to evaluate the antioxidant activities of shikonin in vitro. Neurological deficit, infarct size, histopathology changes and oxidative stress markers were evaluated after 22h of reperfusion. In comparison with the model group, treatment with shikonin significantly decreased neurological deficit scores, infarct size, the levels of malondialdehyde(MDA), carbonyl and reactive oxygen species, and attenuated neuronal damage, up-regulated superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) activities and reduced glutathione (GSH)/glutathione disulfide (GSSG) ratio. Taken together, these results suggested that the neuroprotective effects of shikonin against cerebral ischemia/reperfusion injury may be attributed to its antioxidant effects.
 ...
PMID:Shikonin protects mouse brain against cerebral ischemia/reperfusion injury through its antioxidant activity. 2059 18

Epidemiological studies indicate that the intake of Mediterranean-style diet is inversely associated with risk of stroke, cardiovascular diseases, and cancer. Spirulina is widely used nutritional supplement rich in proteins and antioxidants. Evidence demonstrates that the impaired energy metabolism and the excessive generation of reactive oxygen radicals contribute to the brain injury associated with cerebral ischemia. In the present study, the protective effect of Spirulina was investigated in transient middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia-reperfusion injury in rats. Male albino rats were divided into six groups: control, sham-operated group, ischemic control group, and Spirulina-pretreated groups (45, 90 and 180 mg/kg/p.o.). Spirulina was administered once a day, for 7 days. The rats were subjected to a 2-h right MCAO via the intraluminal filament technique and 22 h of reperfusion. Pretreatment with Spirulina significantly reduced the histological changes and neurological deficits. Spirulina at a dose of 180 mg/kg significantly reversed the elevated brain malondialdehyde (MDA) content and restored the decreased activities of brain superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) indicating that Spirulina has the protective potential against cerebral ischemia injury and its protective effects may be due to its antioxidant property.
 ...
PMID:Neuroprotective effect of Spirulina in cerebral ischemia-reperfusion injury in rats. 2070 Jun 12

Mitochondrial dysfunctions generating from cerebral ischemia-reperfusion exert a potential threat on neuronal cell survival and hence, accelerate the aging process and age dependent neuropathology. Thirty min moderate cerebral ischemia induced by bilateral common carotid artery occlusion (BCCAO) followed by 30 min reperfusion caused an increased diene production, depleted glutathione (GSH) content, reduced superoxide dismutase (SOD) and catalase activities and pyramidal neuronal loss in young (2 months old) and aged (20 months old) rat brain compared to sham operated controls. Cytidine 5' diphosphocholine (CDP-Choline) is a known neuroprotective drug. CDP-Choline after metabolism in the liver suffers hydrolysis and splits into cytidine and choline before entering systemic circulation and hardly circumvents blood brain barrier (BBB) as such. Previous reports show CDP-Choline liposomes significantly increased in vivo uptake compared to "free drug" administration in cerebral ischemia. To enhance the therapeutic concentration build up in brain we sought to formulate mannosylated liposomal CDP-Choline (MLCDP) utilizing the mannose receptors. We tested the therapeutic supremacy of MLCDP over liposomal CDP-Choline (LCDP) in global moderate cerebral ischemia reperfusion induced neuronal damage. CDP-Choline in MLCDP delivery system was found potent to exert substantial protection against global moderate cerebral ischemia reperfusion induced mitochondrial damage in aged rat brain. Membrane lipid peroxidation, GSSG/GSH ratio and reactive oxygen species (ROS) generation in cerebral tissue were found to be higher in aged, compared to young rat. Further decline of those parameters was observed in aged rat brain by the induction of global moderate cerebral ischemia and reperfusion. MLCDP treatment when compared to free or LCDP treatment prevented global moderate cerebral ischemia-reperfusion induced mitochondrial damage as evident ultra structurally and release of cytochrome c (cyt c) from mitochondria into cytosol and protected mitochondria to restore its normal structure and functions.
 ...
PMID:Mannosylated liposomal cytidine 5' diphosphocholine prevent age related global moderate cerebral ischemia reperfusion induced mitochondrial cytochrome c release in aged rat brain. 2088 46

Cerebral ischaemia is a leading cause of death and disability. The objective of the present investigation was to explore the neuroprotective potentials of candesartan and atorvastatin alone and their combination against the cerebral ischaemia induced behavioral, biochemical, and mitochondrial dysfunction. Male Wistar rats (200-220 g) were subjected to bilateral common carotid artery occlusion for 30 min followed by 24 h reperfusion. Candesartan (0.1 and 0.3 mg/kg) and atorvastatin (10 and 20 mg/kg) were pretreated for 7 days before animals were subjected to ischaemia reperfusion injury. Various behavioral tests (locomotor activity and rotarod performance), biochemical parameters (Malondialdehyde levels, nitrite concentration, superoxide dismutase and catalase activity, redox ratio, and GST) and mitochondrial enzyme (Complex I, II, III, and IV) dysfunctions were measured in cerebral cortex, striatum and hippocampus of the ischaemic brain. Seven days candesartan (0.1 and 0.3 mg/kg) or atorvastatin (10 and 20 mg/kg) pretreatment significantly attenuated neurobehavioral alterations, oxidative damage and restored mitochondrial enzyme dysfunction as compared to control (I/R) group. Further, combined treatment of candesartan (0.1 mg/kg) and atorvastatin (10 mg/kg) significantly potentiated their protective effect which was significant as compared to their effect alone. Present study suggests the protective effect of candesartan and atorvastatin and their combination against ischaemia reperfusion induced behavioral and biochemical alterations in rats.
 ...
PMID:Neuroprotective potentials of candesartan, atorvastatin and their combination against stroke induced motor dysfunction. 2106 Oct 73


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>