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

There is evidence that the excessive generation of reactive-oxygen radicals contributes to the brain injury associated with transient, cerebral ischemia. This study investigates the effects of tempol, a small, water-soluble molecule, that crosses biological membranes, on the brain injury caused by bilateral occlusion and reperfusion of both common carotid arteries in the gerbil (BCO). Treatment of gerbils with tempol (30 mg/kg i.p. at 30 min prior to reperfusion and at 1 and 6 h after the onset of reperfusion) reduced the formation of post-ischemic brain oedema. Tempol also attenuated the increase in the cerebral levels of malondialdehyde (MDA) and the hippocampal levels of myeloperoxidase (MPO) caused by cerebral ischemia and reperfusion. The immunohistochemical analysis of the hippocampal region of brains subjected to ischemia-reperfusion exhibited positive staining for nitrotyrosine (an indicator of the generation of peroxynitrite) and poly(ADP-ribose) synthetase (PARS) (an indicator of the activation of this nuclear enzyme secondary to single strand breaks in DNA). In gerbils subjected to BCO, which were treated with tempol, the degree of staining for nitrotyrosine and PARS was markedly reduced. Tempol increased survival and reduced the hyperactivity (secondary to the ischemia-induced neurodegeneration) caused by cerebral ischemia and reperfusion. The loss of neurons from the pyramidal layer of the CA1 region caused by ischemia and reperfusion was also attenuated by treatment of gerbils with tempol. This is the first evidence that the membrane-permeable, radical scavenger tempol reduces the cerebral injury caused by transient, cerebral ischemia in vivo.
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PMID:Effects of tempol, a membrane-permeable radical scavenger, in a gerbil model of brain injury. 1096 3

Free radicals appear to participate in the final common pathway of neuronal death in ischemia and may therefore be an adequate target for therapy. Tempol is a nitroxide antioxidant with proven protective efficacy in several animal models, including myocardial ischemia, that has not been previously tested in models of permanent cerebral ischemia. Spontaneously hypertensive rats underwent permanent middle cerebral artery occlusion (PMCAO). Following dose-response and time-window-finding experiments rats were given vehicle or tempol (50 mg/kg) subcutaneously 1 h after PMCAO (n = 10/group). Five animals in each group were evaluated with a motor scale 24 h after the infarct and were then sacrificed and the injury volume was measured. The remaining animals were examined daily with the motor scale and also with a Morris water maze test on days 26-30 after PMCAO and sacrificed on day 30. Motor scores at all time points examined were significantly better in the tempol-treated animals (P < 0.05 for all). Significantly better performance in the water maze test for performance on days 26-30 was noted in the tempol group compared with the vehicle-treated group (P < 0.05). Injury volumes at days 1 and 30 were significantly reduced in the tempol group (9.83 +/- 1.05 vs 19.94 +/- 1.43% hemispheric volume, P = 0.0009, and 13.2 +/- 2.97 vs 24.4 +/- 2.38% hemispheric volume, P = 0.02, respectively). In conclusion, treatment with tempol led to significant motor and behavioral improvement and reduced injured tissue volumes both in the short and in the long term after stroke.
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PMID:The nitroxide antioxidant tempol is cerebroprotective against focal cerebral ischemia in spontaneously hypertensive rats. 1235 77

Decreased cerebral blood flow, hence decreased oxygen and glucose, leads to ischemic brain injury via complex pathophysiological events, including excitotoxicity, mitochondrial dysfunction, increased intracellular Ca2+, and reactive oxygen species (ROS) generation. Each of these could also contribute to cerebral edema, which is the primary cause of patient mortality after stroke. In vitro brain slices are widely used to study ischemia. Here we introduce a slice model to investigate ischemia-induced edema. Significant water gain was induced in coronal slices of rat brain by 5 min of oxygen and glucose deprivation (OGD) at 35 degrees C, with progressive edema formation after return to normoxic, normoglycemic medium. Edema increased with increasing injury severity, determined by OGD duration (5-30 min). Underlying factors were assessed using glutamate-receptor antagonists (AP5/CNQX), blockade of mitochondrial permeability transition [cyclosporin A (CsA) versus FK506], inhibition of Na+/Ca2+ exchange (KB-R7943), and ROS scavengers (ascorbate, Trolox, dimethylthiourea, Tempol). All agents except KB-R7943 and FK506 significantly attenuated edema when applied after OGD; KB-R7943 was effective when applied before OGD. Significantly, complete prevention of ischemia-induced edema was achieved with a cocktail of AP5/CNQX, CsA and Tempo applied after OGD, which demonstrates the involvement of multiple, additive mechanisms. The efficacy of this cocktail further shows the potential value of combination therapies for the treatment of cerebral ischemia.
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PMID:Brain edema induced by in vitro ischemia: causal factors and neuroprotection. 1278 60

The role of the renin-angiotensin system in cognitive impairment is unclear. This work was undertaken to test our hypothesis that renin-angiotensin system may contribute to cognitive decline and brain damage caused by chronic cerebral ischemia. C57BL/6J mice were subjected to bilateral common carotid artery stenosis with microcoil to prepare mice with chronic cerebral hypoperfusion, a model of subcortical vascular dementia. The effects of aliskiren, a direct renin inhibitor, or Tempol, a superoxide scavenger, on brain damage and working memory in these mice were examined. Chronic cerebral hypoperfusion significantly increased brain renin activity and angiotensinogen expression in C57BL/6J mice, which was attributed to the increased renin in activated astrocytes and microvessels and the increased angiotensinogen in activated astrocytes in white matter. Aliskiren pretreatment significantly inhibited brain renin activity and ameliorated brain p67(phox)-related NADPH oxidase activity, oxidative stress, glial activation, white matter lesion, and spatial working memory deficits in C57BL/6J mice with bilateral common carotid artery stenosis. To elucidate the role of oxidative stress in brain protective effects of aliskiren, we also examined the effect of Tempol in the same mice with bilateral common carotid artery stenosis. Tempol pretreatment mimicked the brain protective effects of aliskiren in this mouse model. Posttreatment of mice with aliskiren or Tempol after bilateral common carotid artery stenosis also prevented cognitive decline. In conclusion, chronic cerebral hypoperfusion induced the activation of the brain renin-angiotensin system. Aliskiren ameliorated brain damage and working memory deficits in the model of chronic cerebral ischemia through the attenuation of oxidative stress. Thus, direct renin inhibition seems to be a promising therapeutic strategy for subcortical vascular dementia.
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PMID:Attenuation of brain damage and cognitive impairment by direct renin inhibition in mice with chronic cerebral hypoperfusion. 2185 61