Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemoglobin (Hb) has been demonstrated to be neurotoxic when injected into the cerebral cortex in vivo. However, associated systemic factors such as ischemia and epileptogenesis have limited investigations of Hb toxicity in the intact central nervous system (CNS). In this study, the neurotoxicity of human Hb was assessed in mixed neuronal and glial neocortical cell cultures derived from fetal mice. Exposure of cultures to Hb for 24-28 h produced widespread and concentration-dependent neuronal death (EC50 1-2.5 microM), without injuring glia. Brief exposures (1-2 h) were not toxic. Neuronal death was completely blocked by the 21-aminosteroid U74500A, the antioxidant Trolox, and the ferric iron chelator deferoxamine. The results of these experiments suggest that, in this system, Hb is a potent neurotoxin, and that Hb neurotoxicity may contribute to secondary injury processes after trauma and intracranial hemorrhage.
 ...
PMID:Neurotoxicity of hemoglobin in cortical cell culture. 832 97

Substantial generation of oxygen-derived free radicals has been implicated in pathophysiology of ischemic brain damage. Immunoreactive mitochondrial manganese and cytosolic copper-zinc superoxide dismutases, initial and essential enzymes to scavenge superoxide radical anions, increased in the gerbil hippocampal neurons after transient forebrain ischemia. Neuronal cells responded to oxidative stress in ischemia and induced the protective mechanism to increase superoxide dismutases.
 ...
PMID:Effect of transient forebrain ischemia on superoxide dismutases in gerbil hippocampus. 836 63

Excessive intracellular accumulation of calcium has been postulated to result in ischemic neuronal death. Reduction of intracellular calcium entry should therefore be expected to reduce ischemic neuronal injury. Two pathways through which extracellular calcium ions can enter neurons are voltage-sensitive and N-methyl-D-aspartate receptor-linked cation pores. Combined blockade of both these types of channels might be more effective in reducing intracellular calcium accumulation than the blockade of either channel alone. We therefore evaluated the cerebroprotective effects of dizocilpine, an N-methyl-D-aspartate receptor antagonist, and levemopamil, a phenylalkylamine calcium channel blocker, administered singly or in combination, in a model of forebrain ischemia in the rat. Four groups of rats (n = 8 each) were studied. In the first group, dizocilpine, 5 mg/kg, was administered before ischemia. In the second group, levemopamil, 5 mg/kg, was given both preischemia and 2 h postischemia. In the third group, both dizocilpine (5 mg/kg) and levemopamil (5 mg/kg) were given preischemia and levemopamil (5 mg/kg) was given postischemia. The control group received saline placebo. The rats were subjected to forebrain ischemia by bilateral carotid artery occlusion for 10 min with simultaneous hypotension to 35 mm Hg. Neuronal injury was evaluated 3 days after ischemia. Dizocilpine reduced postischemia neuronal injury in the ventral hippocampus (p = 0.045). Levemopamil and the combination of levemopamil and dizocilpine did not protect neurons from ischemic injury. The present study does not provide support for the strategy of combined therapy with dizocilpine (administered before ischemia) and levemopamil (administered before and after ischemia) to protect neurons from injury produced by severe incomplete forebrain ischemia.
 ...
PMID:Combined therapy with dizocilpine and levemopamil does not reduce ischemic neuronal injury in rats. 840 Jul 59

Post-ischemic treatment of di-Calciphor (16,16'-dimethyl-15- dehydroprostaglandin B1) significantly improves animal survival and prevents ischemia-induced neurodegeneration of vulnerable forebrain regions assessed with histochemical and biochemical techniques in gerbils. Neuronal degeneration seen by Cresyl violet staining and silver impregnation in the CA1 sector of the hippocampus and the dorso-lateral sector of the striatum was significantly reduced in animals treated with di-Calciphor. In addition, the early onset of selective degradation of calpain I substrates spectrin and microtubule-associated protein (MAP2) in these same vulnerable regions was prevented. The lack of adverse side effects may facilitate the potential therapeutic use of this drug in preventing neuronal damage caused by stroke.
 ...
PMID:Neuroprotective activity of dimer of 16,16'-dimethyl-15-dehydroprostaglandin B1 (di-Calciphor) in cerebral ischemia. 846 94

Neuronal uptake1 constitutes the main elimination process of cardiac norepinephrine under normoxic conditions. Uptake1 may be subject to changes during myocardial ischemia. We therefore studied the regulation of the uptake1 carrier in isolated perfused rat hearts, comparing ischemic and nonischemic conditions. Radioligand binding with [3H]mazindol was used to determine carrier densities and affinities, whereas cardiac clearance of[3H]norepinephrine served as a measure of the transport capacity of the uptake1 carrier. When exocytotic norepinephrine release was induced in nonischemic rat hearts by electrical field stimulations, we observed an increase in the cardiac density of uptake1 carriers (Bmax) to 210 +/- 5 fmol/mg protein (versus 134 +/- 3 fmol/mg in control hearts). Simultaneously, the cardiac clearance of [3H]norepinephrine increased to 41 +/- 4% versus 30 +/- 4% in control hearts. Both carrier density and norepinephrine clearance returned to baseline values within a period of 40 minutes after stimulation. Carrier affinities (Kd values) did not differ between the groups. Stop-flow ischemia induced a substantial overflow of norepinephrine by itself. Additionally, carrier density was increased to 144% after 40 minutes of stop-flow ischemia (P < .005 versus control hearts). When ischemia was followed by 20 minutes of reperfusion, the Bmax of the uptake1 carrier remained significantly elevated. With a further extension of the reperfusion period to 40 minutes, however, carrier density declined to baseline values. Kd values were not influenced by any of these interventions. Clearance of [3H]norepinephrine was suppressed (to 5 +/- 2%) in the first minutes of reperfusion, which may reflect the inverse transport direction of the norepinephrine carrier known to occur in ischemia. After 20 minutes of reperfusion, clearance increased to 39 +/- 5% (P < .005 versus control hearts) and then fell to 29 +/- 5% after 40 minutes of reperfusion (NS). These results demonstrate that after both electrical field stimulation and myocardial ischemia, the density of uptake1 carrier proteins temporarily increases, which may result in an increased transport capacity for norepinephrine.
 ...
PMID:Upregulation of cardiac uptake 1 carrier in ischemic and nonischemic rat heart. 863 34

Progression of ischemic damage was investigated immunohistochemically in neural dendrites using microtubule-associated protein 2 (MAP2) as a dendritic marker in the rat's brainstem. Neuronal soma and dendrites were clearly stained by this protein but some structures such as axonal bundles, glia and endothelial cells were not visualized. When the anterior inferior cerebellar artery (AICA) was occluded unilaterally for 30 min, a wide ischemic lesion was detected in the occluded side of the brainstem and was observed as a loss of reaction to MAP2. After ischemia for 2 h, loss of reaction in the perikarya and dendrites was seen to expand to the ipsilateral (occluded side) cochlear nucleus. When the basilar artery was blocked, ischemic damage in the vestibular nucleus was more intense than that in the cochlear nucleus. In all specimens studied, differences in anatomical blood supply demonstrated selective tissue vulnerability for ischemic damage.
 ...
PMID:Brainstem ischemic damage following occlusion of the blood vessels in the rat's posterior cerebral circulation. 865 61

Dichloroacetate (DCA) activates the pyruvate dehydrogenase complex (PDHC), and improves the recovery of cerebral pH, lactate, ATP, and PCr following reperfusion in animal models of forebrain ischemia. In order to determine whether this results in neuroprotection, rats were administered NaDCA (100 mg/kg or 10mg/kg i.v.) 10 min before 12 min of normothermic forebrain ischemia (bilateral carotid artery occlusion plus systemic hypotension, 45 mmHg). Neuronal injury assessed histopathologically 7 days post-ischemia was significantly reduced in the CA1 region of the hippocampus, the dorsal lateral striatum, and the neocortex, in rats treated with 100 mg/kg NaDCA, but not in rats treated with 10 mg/kg NaDCA.
 ...
PMID:Protective effect of dichloroacetate in a rat model of forebrain ischemia. 873 Nov 65

In this study the effect of memantine, an antagonist at the N-methyl-D-aspartate receptor, on spatial learning deficit and on neuronal damage following transient cerebral ischemia was evaluated. Global ischemia was induced by four-vessel-occlusion (4VO) for 20 min in rats. Memantine was administered 20 min before induction of ischemia at a dose of 10 or 20 mg/kg. One week after surgery spatial learning was tested in the Morris water maze. Treatment with the higher dose of memantine reduced the increase in escape latency and in swim distance induced by 4VO. Neuronal damage in the CA1 sector of the hippocampus and in the striatum produced by 4VO was significantly attenuated by 20 mg/kg memantine. Treatment with the lower dose of memantine had no influence on the deficit in spatial learning and the neuronal damage resulting from ischemia. The present data demonstrate that treatment with a neuroprotective agent like memantine can reduce functional as well as morphological sequelae induced by ischemia.
 ...
PMID:Memantine reduces functional and morphological consequences induced by global ischemia in rats. 873 Nov 70

Microglial and astrocyte responses to glucocorticoid pretreatment in the neonate exposed to hypoxia-ischemia (HI) are largely unknown. The expression of microglial antigens and astrocytic proliferation was compared in neonatal rats exposed to HI with and without cortisone. HI was induced in 7 day old rats. One group of rats received cortisone within 24 h of birth. Immunocytochemical and immunoblot investigations were performed. Monoclonal antibodies (OX18 and OX42) were used for the detection of the major histocompatibility complex (MHC) class I antigens and complement receptor 3 (CR3) respectively. Antibodies directed against glial fibrillary acidic protein (GFAP) and microtubule associated protein II (MAP II) were used to evaluate the extent of brain damage. Cortisone treatment provoked a decline in the number of microglial cells but did not modify GFAP levels in control rats which were not exposed to HI. Neuronal damage was similar in control and cortisone treated rats exposed to HI. There were also similarities in the expression of CR3 antigens on microglia. However microglial cells expressing MHC class I antigens were less prevalent in rats exposed to HI only. Cortisone pretreatment enhanced the expression of MHC class I antigens. Astrocytic proliferation was intense in rats exposed to HI; however in rats treated with cortisone and exposed to HI there was a drastic reduction in astrocytic proliferation. In conclusion it is suggested that microglia which survive cortisone pretreatment become over-activated thereby preventing astrocytic proliferation.
 ...
PMID:Microglia-astrocyte interactions after cortisone treatment in a neonatal hypoxia-ischemia model. 881 76

Glutamate antagonists have been shown to be neuroprotective in animal models of cerebral ischemia. Global cerebral ischemia in rats leads to selective neuronal damage in the hippocampus and striatum. Following ischemia a deficit in spatial learning and memory occurs. The aim of the present study was to investigate the potential neuroprotective effect of GYKI 52466, an antagonist at the non-N-methyl-D-aspartate receptor, with behavioural and histological measures of global ischemia in rats. Global ischemia was induced by four-vessel-occlusion (4VO) for 20 min in rats. GYKI 52466 (30 mg/kg i.p.) was administered either 20 min before induction of ischemia or immediately after onset of reperfusion. One week after surgery spatial learning was tested in the Morris water maze. After behavioural testing the animals were sacrificed and the neuronal damaged was assessed. GYKI 52466 reduced the increase in escape latency and in swim distance induced by 4VO when given before ischemia but not when applied after ischemia. Neuronal damage in the CA1 sector of the hippocampus produced by 4VO was significantly attenuated by pretreatment but not by posttreatment with GYKI 52466. Striatal neuronal damage was not affected by either treatment with GYKI 52466. GYKI 52466 had neuroprotective effects in a rat model of global cerebral ischemia. Pretreatment with GYKI 52466 protected rats against behavioural deficits and hippocampal neuronal damage induced by 4VO.
 ...
PMID:Pretreatment but not posttreatment with GYKI 52466 reduces functional deficits and neuronal damage after global ischemia in rats. 885 48


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