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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental stroke using a focal cerebral ischemia and reperfusion (FCIR) model was induced in male Long-Evans rats by a bilateral occlusion of both common carotid arteries and the right middle cerebral artery for 30-90 min, followed by various periods of reperfusion. Oxidative DNA lesions in the ipsilateral cortex were demonstrated using Escherichia coli formamidopyrimidine DNA N-glycosylase (Fpg protein)-sensitive sites (FPGSS), as labeled in situ using digoxigenin-dUTP and detected using antibodies against digoxigenin. Because Fpg protein removes 8-hydroxy-2'-deoxyguanine (oh8dG) and other lesions in DNA, FPGSS measure oxidative DNA damage. The number of FPGSS-positive cells in the cortex from the sham-operated control group was 3 +/- 3 (mean +/- SD per mm(2)). In animals that received 90 min occlusion and 15 min of reperfusion (FCIR 90/15), FPGSS-positive cells were significantly increased by 200-fold. Oxidative DNA damage was confirmed by using monoclonal antibodies against 8-hydroxy-guanosine (oh8G) and oh8dG. A pretreatment of RNase A (100 microg/ml) to the tissue reduced, but did not abolish, the oh8dG signal. The number of animals with positive FPGSS or oh8dG was significantly (P<0.01) higher in the FCIR group than in the sham-operated control group. We detected few FPGSS of oh8dG-positive cells in the animals treated with FCIR of 90/60. No terminal UTP nicked-end labeling (TUNEL)-positive cells, as a detection of cell death, were detected at this early reperfusion time. Our data suggest that early oxidative DNA lesions elicited by experimental stroke could be repaired. Therefore, the oxidative DNA lesions observed in the nuclear and mitochondrial DNA of the brain are different from the DNA fragmentation detected using TUNEL.
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PMID:Oxidative DNA damage precedes DNA fragmentation after experimental stroke in rat brain. 1078 50

Levels of endothelin-1 (ET-1), a potent endogenous vasoconstrictor, are elevated in plasma and cerebrospinal fluid (CSF) following cerebral ischemia and reperfusion injury. The present study sought insight into the potential differential vasoactive effects on the cerebral vasculature and resultant neural damage of ET-1 during normoxic vs. ischemic conditions and upon reperfusion. Under normoxic conditions, intrastriatal stereotaxic injection of exogenous ET-1 (40 pmol) induced a significant (P<0.05) reduction (</=29+/-12%) in the regional (striatal) cerebral blood flow measured by Laser Doppler flowmetry (CBF(LDF)) for up to 40 min in halothane-anesthetized male Long-Evans rats. Intrastriatal injection of ET-1 10 min after the onset of hypoxia (12% O(2), balance N(2)) tended to blunt, but not significantly, the striatal CBF(LDF) responses to the 35 min period of hypoxia. ET-1 given during reoxygenation significantly (P<0.05) reduced striatal CBF(LDF), which was similar to the effect of ET-1 during normoxia. ET-1-induced infarction when administered prior to hypoxia, but not during or post-hypoxia, was significantly (P<0.05) exacerbated compared to infarction of ET-1 without hypoxia. These results suggest that exogenous ET-1 administered into the brain parenchyma can induce an infarction associated with modulation of CBF(LDF) during the normoxic or reoxygenation period, but not during the hypoxic period and that the increased release of ET-1 in any pathological phase of cerebral ischemia contributes to irreversible neural damage with associated hemodynamic disturbances.
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PMID:Hypoxic modulation of striatal lesions induced by administration of endothelin-1. 1106 87

The effects of hexasulfobutylated C60 (FC4S), a free radical remover, on the total volume infarct size elicited by the damaging effects of focal cerebral ischemia were studied on Long-Evans rats in vivo. FC4S was administered intravenously either 15 min before middle cerebral artery (MCA) occlusion (pretreatment groups) or it was injected when the common carotid arteries clips were removed (treatment groups). FC4S did not alter the pH, blood gases, heart rate, or mean arterial blood pressure in either pretreatment or treatment groups of the rats. However, after administration of FC4S at dosages of 10 and 100 microg/kg, the total volume of infarction was significantly reduced in both pretreatment and treatment groups. In addition, after FC4S administration, the nitric oxide (NO) content in plasma was increased and the lactate dehydrogenase (LDH) levels was decreased. It is concluded that FC4S may be used as a neuroprotective agent on focal cerebral ischemia. The beneficial effects may be partly related to its antioxidant property and to the upregulation of NO production of the compound.
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PMID:Neuroprotective effect of hexasulfobutylated C60 on rats subjected to focal cerebral ischemia. 1129 62

In patients with thrombotic stroke, the occluded artery often reopens over time. This results through a natural dissolution of the occluding material, and fragments of the material may move downstream to obstruct distal arteries. The current study was undertaken to investigate the patency of brain microvessels at varying time intervals after injection of a preformed clot into the right internal carotid artery of rats. Cerebral microvessels in brain sections were visualized using immunohistochemistry for fibronectin (detecting existing microvessels) and Evans blue (visualizing perfused microvessels). The percentage of patent microvessels was calculated as the number of Evans blue-positive microvessels divided by the number of fibronectin-positive microvessels. In normal control animals, results showed that 98% +/- 3% (mean +/- SD) of microvessels in the cortex and 94% +/- 14% in the striatum were patent. In the ischemic animals, immediately after clot injection, microvessels in the cortex and striatum were occluded, mainly in the territory irrigated by the middle cerebral artery. One hour after clot injection, microvessels had reopened in most of the cortex but remained occluded in some portions of the striatum, possibly as a result of downstream movement of fragments formed from the original clot. By 3 hours after clot injection, microvessels in the cortex were patent in all animals, whereas in the striatum microvessels were patent in 50% of the animals. In the other 50%, small striatal perfusion deficits persisted. At 24 hours after clot injection, microvessels were patent in both the cortex and striatum of all animals except one. These findings suggest that intracerebral clots dissolve spontaneously in a relatively short period of time, but that fragments formed from the clot may obstruct more distal blood vessels. It is likely that clot fragments lodge in arteries with lower blood flow and poor collateral perfusion, where they continue to cause ischemia for a longer duration. These results may in part explain the resistance of the striatum to neuroprotective strategies used for the treatment of focal cerebral ischemia.
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PMID:Patency of cerebral microvessels after focal embolic stroke in the rat. 1132 27

In response to oxidative stress, the ischemic brain induces immediate early genes when its nuclear genes contain gene damage. Antioxidant that reduces gene damage also reduces cell death. To study the mechanism of neuronal sensitivity, we investigated the transcription of the c-fos gene after brain injury of the ischemia-reperfusion type using focal cerebral ischemia-reperfusion in Long-Evans hooded rats. We observed a significant (p < 0.01) increase in c-fos mRNA in the ischemic cortex immediately after brain injury. However, the c-fos transcript was sensitive to RNase A protection assay (RPA) upon reperfusion. The transcript became significantly resistant to RPA (42%, p < 0.03) when 3-bromo-7-nitroindazole (25 mg/kg, i.p.), known to abolish nitric oxide, gene damage and neuronal sensitivity, was injected. Our data suggest that neuronal nitric oxide synthase and aberrant mRNA from genes with oxidative damage could be associated with neuronal sensitivity.
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PMID:Neuronal NOS inhibitor that reduces oxidative DNA lesions and neuronal sensitivity increases the expression of intact c-fos transcripts after brain injury. 1145 96

Resveratrol is found in a wide variety of plant species. It is present in the seeds and skin of grapes and constitutes one of the major components of red wine. This study was undertaken to evaluate whether resveratrol could effectively suppress infarct size from the damaging effects of focal cerebral ischemia. The middle cerebral artery was occluded for 1 hr and 24 hr reperfusion in anesthetized Long-Evans rats. In pretreatment or treatment groups, resveratrol, at dosages of 10(-6), 10(-7), 10(-8) and 10(-9) g/kg, was intravenous injected 15 minutes before middle cerebral artery (MCA) occlusion or when the common carotid arteries clips were removed respectively. Pretreatment or treatment of resveratrol (10(-6), 10(-7), 10(-8) and 10(-9) g/kg) did not produce any changes in pH, blood gases, heart rate or mean arterial blood pressure, but it significantly reduced the total volume of infarction at the doses 10(-6) and 10(-7) g/kg. Our study suggests resveratrol is a potent neuroprotective agent in focal cerebral ischemia. Its beneficial effects may be related to its anti-platelet aggregation activity, vasodilating effect, antioxidant property or by all mechanisms together.
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PMID:Resveratrol reduction of infarct size in Long-Evans rats subjected to focal cerebral ischemia. 1150 48

Magnesium probably protects brain tissue against the effects of cerebral ischemia, brain injury and stroke through its actions as a calcium antagonist and inhibitor of excitatory amino acids. The effects of magnesium sulfate on cerebrovascular permeability to a dye, Evans blue, were studied during insulin-induced hypoglycemia with hypothermia in rats. Hypoglycemia was induced by an intramuscular injection of insulin. After giving insulin, each animal received MgSO4 (270 mg/kg) ip, followed by a 27 mg/kg dose every 20 min for 2.5 h. Plasma glucose and Mg2+ levels of animals were measured. Magnesium concentrations increased in the serum following MgSO4 administration (6.05+/-0.57 vs. 2.58+/-0.14 mg/dL in the Mg2+ group, and 7.14+/-0.42 vs. 2.78+/-0.06 mg/dL in the insulin + Mg2+ group, P < 0.01). Plasma glucose levels decreased following hypoglycemia (4+/-0.66 vs. 118+/-2.23 mg/dL in the insulin group, and 7+/-1.59 vs. 118+/-4.84 mg/dL in the insulin + Mg2+ group, P < 0.01). Blood-brain barrier permeability to Evans blue considerably increased in hypoglycemic rats (P < 0.01). In contrast, blood-brain barrier permeability to Evans blue was significantly reduced in treatment of hypoglycemic rats with MgSO4 (P < 0.01). These results indicate that Mg2+ greatly reduced the passage of exogenous vascular tracer bound to albumin into the brain during hypoglycemia with hypothermia. Mg2+ could have protective effects on blood-brain barrier permeability against insulin-induced hypoglycemia.
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PMID:Magnesium sulfate attenuates increased blood-brain barrier permeability during insulin-induced hypoglycemia in rats. 1159 80

We have previously described a rodent model of brief (30 min) middle cerebral artery occlusion followed by reperfusion, in which infarction develops gradually, reaching completion more than 3 days after ischemia, accompanied by morphological, biochemical, and pharmacological evidence of apoptosis. In the present study, we tested the hypotheses that delayed administration of a protein synthesis inhibitor would be effective in reducing tissue injury in this slowly evolving ischemic infarction, and that efficacy of this treatment would wane with more prolonged ischemia. Focal cerebral ischemia was induced in Long-Evans rats by occlusion of the right middle cerebral artery. Infarction volume was analyzed using triphenyl tetrazolium chloride staining, and morphology was studied using hematoxylin and eosin stained sections. Following 30 min middle cerebral artery occlusion and reperfusion, the core ischemic region exhibited vacuolization in the neuropil by 36 h after ischemia, and infarction reached full size by 7 days after ischemia. Cycloheximide reduced infarct volume when given up to 6 h after ischemia. If the duration of ischemic insult was increased to 90 min, the therapeutic window for delayed cycloheximide was only 30 min. In permanent middle cerebral artery occlusion, cycloheximide was ineffective even when given prior to ischemia onset. After mild, but not severe, ischemic insults, cerebral infarction develops slowly and may be treatable with protein synthesis inhibitors, even when treatment is delayed for up to 6 h after the onset of ischemia.
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PMID:Cycloheximide reduces infarct volume when administered up to 6 h after mild focal ischemia in rats. 1164 Sep

The role of nitric oxide (NO) in the development of post-ischemic cerebral infarction has been extensively examined, but fewer studies have investigated its role in other outcomes. In the present study, we first determined the temporal evolution of infarct volume, NO production, neurological deficit and blood-brain barrier disruption in a model of transient focal cerebral ischemia in mice. We then examined the effect of the nonselective NO-synthase inhibitor N(omega)-nitro-L-arginine-methylester (L-NAME). L-NAME given at 3 mg/kg 3 h after ischemia reduced by 20% the infarct volume and abolished the increase in brain NO production evaluated by its metabolites (nitrites/nitrates) 48 h after ischemia. L-NAME with this protocol also reduced the neurological deficit evaluated by the grip test and decreased by 65% the extravasation of Evans blue, an index of blood-brain barrier breakdown. These protective activities of L-NAME suggest that NO has multiple deleterious effects in cerebral ischemia.
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PMID:L-NAME reduces infarction, neurological deficit and blood-brain barrier disruption following cerebral ischemia in mice. 1246 59

Melatonin is a potent antioxidant and free radical scavenger. Previously, we showed that a single injection of melatonin before ischemia significantly reduced the infarct volume in both permanent and 3-hr middle cerebral artery occlusion (MCAO) rat stroke models. Nitric oxide (NO) and other free radicals play an important role in the pathogenesis of cerebral ischemia, and they have been postulated to mediate the breakdown of the blood-brain barrier (BBB) during ischemia. In this study, we evaluated the influence of melatonin, given at 30 min before MCAO, on brain NO concentration and BBB breakdown. Brain NO concentration was measured at 15 min of MCAO using electron paramagnetic resonance spectroscopy. BBB breakdown at 3 hr of reperfusion following 3 hr of MCAO was assessed using Evans blue extravasation. The relative brain NO concentration was increased to 141.69 +/- 9.71% (mean +/- S.E.M.; n = 9) at 15 min of MCAO. Treatment with melatonin at 1.5, 5, or 50 mg/kg significantly reduced the brain NO concentration to 104.20 +/- 11.20% (n = 8), 55.67 +/- 5.58% (n = 11), and 104.86 +/- 12.56% (n = 9), respectively. Melatonin at 5 mg/kg did not affect Evans blue extravasation. Our results suggest that a single injection of melatonin protects against focal cerebral ischemia partly via inhibition of ischemia-induced NO production and that this regimen does not prevent BBB breakdown following ischemia-reperfusion.
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PMID:Melatonin reduces nitric oxide level during ischemia but not blood-brain barrier breakdown during reperfusion in a rat middle cerebral artery occlusion stroke model. 1256 2


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