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

Copper-zinc-superoxide dismutase (CuZn-SOD), a cytosolic antioxidant enzyme that is specific for scavenging superoxide radicals, is involved in neuroprotective mechanisms in brain injury following trauma and cerebral ischemia. Liposome-entrapped CuZn-SOD exhibit beneficial effects in vivo on cold-induced vasogenic edema and on blood-brain barrier disruption. The increased levels of edema and infarction following a focal cerebral ischemia also are decreased by the pretreatment of liposome-entrapped CuZn-SOD. The protective role of SOD on brain injury was further extended and confirmed in studies using transgenic mice overexpressing human CuZn-SOD. Our studies so far suggest that increased cerebral levels of SOD, either by means of external pharmacological application or by genetic manipulations, ameliorate brain edema and infarction induced by trauma and focal cerebral ischemia.
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PMID:Antioxidant-dependent amelioration of brain injury: role of CuZn-superoxide dismutase. 131 99

Oxygen-derived free radicals have been implicated in the pathogenesis of vasogenic edema and infarction caused by ischemia and reperfusion injury. In earlier studies, exogenously supplied liposome-entrapped CuZn superoxide dismutase (CuZn-SOD) ameliorated ischemic brain edema and infarction in rats following focal cerebral ischemia. To ascertain directly the role of SOD in the protection against superoxide radical-induced injury, we measured infarct size and water content 24 hr following focal cerebral ischemia in nontransgenic mice and in transgenic mice bearing the human SOD1 gene. These transgenic mice have 3.1-fold higher cellular CuZn-SOD activity in the brain than do their nontransgenic littermates. We also measured antioxidant levels (reduced glutathione and reduced ascorbate) of contralateral cortex, infarct cortex, surrounding cortex, and striatum. Infarct size and brain edema were significantly decreased in transgenic mice compared with nontransgenic mice. Reduced glutathione and reduced ascorbate levels decreased in the ischemic hemisphere, but levels in surrounding cortex and striatum were significantly higher in transgenic mice than in nontransgenic mice. These results indicate that increased endogenous SOD activity in brain reduces the level of ischemic damage and support the concept that superoxide radicals play an important role in the pathogenesis of infarction and edema following focal cerebral ischemia.
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PMID:Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase. 176 30

Oxygen-derived free radicals have been postulated to be involved in brain edema and cell death secondary to ischemia and traumatic injury. Using a model of vasogenic brain edema produced by a permanent occlusion of the left MCA in rats, we have studied the role of superoxide radicals in pathogenesis of ischemic edema. The levels of NBF in ischemic brain were increased by 222%, 420%, and 614%, respectively, at 1, 4, and 24 hr after the MCAO. Topical application of superoxide dismutase to the injured cortex through a modified cranial window significantly reduced the NBF levels, indicating the involvement of superoxide radicals in ischemic brain. Liposome-entrapped SOD, when IV injected 5 min after the MCAO, significantly reduced the degree of edema at 24 hr. Our data indicate that superoxide radicals play an important role in the pathogenesis of vasogenic edema in cerebral ischemia.
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PMID:Pathogenesis of vasogenic edema in focal cerebral ischemia. Role of superoxide radicals. 216 62

Superoxide dismutase and catalase enzymatically scavenge superoxide and hydrogen peroxide, respectively. Conjugation of polyethylene glycol to superoxide dismutase (PEG-SOD) or catalase (PEG-CAT) prolongs the circulatory half-life of the native enzymes and enhances their intracellular access. We studied the protective effect of these free radical scavengers on ischemic brain injury using a rat model of focal cerebral ischemia, which is suitable for therapeutic trials. Intravenous administration of PEG-SOD (10,000 U/kg) and PEG-CAT (10,000 U/kg) before ischemia reduced the infarct volume (treatment, 139 +/- 9 mm3, means +/- SE, N = 38; placebo, 182 +/- 8 mm3, n = 37, P less than 0.002). This finding supports the concept that superoxide and hydrogen peroxide contribute to brain injury following focal cerebral ischemia.
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PMID:Polyethylene glycol-conjugated superoxide dismutase and catalase reduce ischemic brain injury. 249 71

The Central Nervous System (CNS) exhibits a high sensitivity to ionizing radiation from conception until after birth. X-irradiation damage of the nervous system during development has been well documented and exposure to ionizing radiation above approximately 10 cGy during perinatal development is contraindicated. Shielding of the embryo or fetus usually prevents gross malformations but high energy irradiation of the pregnant female may result in embryonic growth retardation. This may be especially true when the irradiation is coupled with an ethanol-induced reduction in SOD activity. The synergistic interactions between other drugs and ionizing radiation also have been demonstrated. However, the concentration of endogenous compounds such as histamine and serotonin may be increased in the maternal circulation following irradiation and reach the fetal CNS through a blood-brain-barrier that is more permiable than normal. The introduction of histamine and/or serotonin into the fetal circulation may result in fetal hypotension, edema, cerebral ischemia, and damage to the developing CNS.
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PMID:Prenatal radiation risk to the brain. 269 98

The activity of the free radical scavenger, superoxide dismutase, was studied in focal cerebral ischemia produced in Mongolian gerbils (Meriones unguiculatus) by occluding the right common and left external carotid arteries under halothane anesthesia. After recovery from anesthesia animals were classified according to their neurologic symptoms. Five animals exhibiting neurologic symptoms such as hemiparesis and rolling seizures were reanesthetized 120 min after vascular occlusion and their brains frozen in situ with liquid nitrogen. A series of 20-micron-thick coronal sections was cut in a cryostat; pictorial representations of tissue pH, ATP, and glucose were obtained using fluorescent and bioluminescent techniques. Using a highly sensitive bioluminescent technique, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and Mn-superoxide dismutase (Mn-SOD) activities were then measured in samples from both ischemic and nonischemic regions of the remaining tissue block. Cu,Zn-SOD and Mn-SOD activities were, respectively, 13.9 +/- 0.7 X 10(3) units/g and 5.4 +/- 0.3 X 10(3) units/g in the nonischemic tissue, and 13.2 +/- 0.6 X 10(3) units/g and 5.0 +/- 0.2 X 10(3) units/g within the ischemic tissue. Thus focal cerebral ischemia does not lead to a global decrease in SOD activity, as observed by others after heart and liver ischemia.
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PMID:Superoxide dismutase activity in experimental focal cerebral ischemia. 406 77

We investigated the changes of copper/zinc superoxide dismutase (CuZn-SOD) and manganese superoxide dismutase (Mn-SOD) in the rat hippocampus after 10 min of cerebral ischemia induced by 4-vessel occlusion. The rats were allowed to survive for 4 h, 1 day, 3 days, and 7 days after ischemia. The distribution of SODs were determined by immunohistochemical staining with antibodies against rat CuZn-SOD and Mn-SOD. CA1 pyramidal neurons and granule cells of the dentate gyrus showed intense CuZn-SOD immunoreactivity, whereas CA3 and CA4 neurons showed weaker immunostaining than CA1 neurons in normal animals. The immunoreactivity was reduced by 4 h after ischemia in CA1, CA3, and CA4 neurons when no histological damage was observed. Mn-SOD immunostaining revealed more intense immunoreactivity in CA3 pyramidal neurons than in CA1 neurons in normal animals. Interneurons in the CA1 and CA3 regions and the dentate hilus also showed high Mn-SOD immunostaining. Although CA1 neurons lost Mn-SOD immunoreactivity by 1 day after ischemia, CA3 neurons and interneurons retained the immunoreactivity and preserved intact cell contour after ischemia. In addition, reactive glial cells, which were differentiated by immunocytochemical staining against glial fibrillary acidic protein for reactive astrocytes and histochemical staining for reactive microglial cells, were intensely stained for CuZn-SOD and Mn-SOD after ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An immunohistochemical study of copper/zinc superoxide dismutase and manganese superoxide dismutase in rat hippocampus after transient cerebral ischemia. 769 76

Bromocriptine, a dopamine D2 receptor agonist, has widely been used for patients with Parkinson's disease. In this study, we examined its neuroprotective effects against neuronal damage in the CA1 subfield of the hippocampus following experimental cerebral ischemia in the Mongolian gerbil. Forebrain ischemia was induced by occlusion of bilateral common carotid arteries for 3 min. Bromocriptine, at a dose of 0.3 or 3 mg/kg, was injected i.p. 30 min before the onset of ischemia. Histopathological observations showed that neuronal damage to hippocampal CA1 neurons, which was seen 7 days after ischemia in vehicle-treated animals, was prevented by bromocriptine treatment. Immunohistochemical staining for copper/zinc superoxide dismutase and manganese superoxide dismutase decreased markedly in the CA1 neurons of vehicle-treated animals 2 days after ischemia when histological neuronal destruction was not yet seen, but was well preserved in bromocriptine-treated animals. The present findings show that bromocriptine protects against ischemia-induced neuronal damage, and that the mechanism of the neuroprotection may relate to the preservation of SODs. Bromocriptine, which was recently shown to be a potent free radical scavenger, may have a potent neuroprotective action against disorders including ischemic stroke.
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PMID:Bromocriptine protects against delayed neuronal death of hippocampal neurons following cerebral ischemia in the gerbil. 775 51

A new histofluorescence method by HPAA (p-hydroxyphenyl acetic acid) for free radicals in the brain tissue was devised to study neuronal damage induced by ischemia. Cerebral ischemia was produced in rats by injection of plastic microspheres and arachidonic acid (AA) into the right carotid artery. The concentration of malondialdehyde (MDA; free radical) in cerebral cortex of aminotriazol (an H2O2-dependent inhibitor of catalase) treated rats 2 h after stroke was 6.33 times the level before infarction, while the concentration of MDA in h-r SOD (free radical-scavenging enzyme) treated rats 2 h after stroke was significantly lower than in untreated rats. The histochemical findings demonstrated marked H2O2 production around blood vessels occluded by microspheres in the cerebral cortex of the aminotriazole treated rats 2 h after stroke together with disruption of the BBB. Light microscopical findings demonstrated extensive edematous changes in the aminotriazole treated rats 2 h after stroke, while pathological damage in SOD treated rat brains was absent or minimal. We conclude that free radicals are formed during ischemia, and that AA appears to be a major source of activated oxygen radicals. The findings indicate that SOD is protective against ischemia-induced neuronal damage.
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PMID:Histochemical demonstration of free radicals (H2O2) in ischemic brain edema and protective effects of human recombinant superoxide dismutase on ischemic neuronal damage. 797 74

Oxygen free radicals have been widely implicated in the pathogenesis of brain injury due to ischemia followed by reperfusion. The success of making transgenic animals overexpressing human CuZn-superoxide dismutase (CuZn-SOD) in brain cells allows researchers to discern the specific role of superoxide radicals in reperfusion injury after focal ischemia. It has been shown that increased brain levels of CuZn-SOD in transgenic mice protect neurons from ischemia/reperfusion injury. However, overexpression of CuZn-SOD does not provide neuronal protection in permanent focal ischemia in mice, when compared with non-transgenic mouse littermates. It is proposed that molecular genetic approaches of modifying antioxidant levels in the brain offer a unique tool for studying oxidative mechanisms in focal cerebral ischemia.
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PMID:Oxygen radicals in focal cerebral ischemia. 802 3


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