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)

A brief interruption of blood flow to the brain results in the selective loss of specific subpopulations of neurons. Important advances have been made in recent years in defining the biochemical changes associated with cerebral ischaemia and reperfusion and in identifying physical and chemical interventions capable of modifying the extent of neuronal loss. Neuronal death is not irreversibly determined by the ischaemic period but develops during recirculation over a period of hours or even days in different susceptible neuronal populations. The onset of ischaemia produces a rapid decline in ATP production and an associated major redistribution of ions across the plasma membrane including a large intracellular accumulation of Ca2+ in many neurons. Alterations subsequently develop in many other metabolites. These include a marked and progressive release of neurotransmitters and a rapid accumulation of free fatty acids. Most of these alterations are reversed within the first 20 min to 1 hr of recirculation. The changes essential for initiating damage in neurons destined to die have not been definitively identified although there is some evidence suggesting roles for the intracellular Ca2+ accumulation, the release of the neurotransmitter glutamate and a brief burst of free radical production which occurs during early recirculation. During further recirculation, there are reductions in oxidative glucose metabolism and protein synthesis in many brain regions. Few changes have been detected which distinguish tissue containing ischaemia-susceptible neurons from ischaemia-resistant regions until the development of advanced degeneration and neuronal loss. Subtle changes in cytoplasmic Ca2+ content and a decrease in the respiratory capacity of mitochondria are two changes apparently selectively affecting ischaemia-susceptible regions which could contribute to neuronal loss. The mitochondrial change may be one indicator of a slowly developing post-ischaemic increase in susceptibility to oxidative damage in some cells.
 ...
PMID:Biochemical changes associated with selective neuronal death following short-term cerebral ischaemia. 767 Nov 33

In this study the effect of an inhibitor of lipid peroxidation and of phospholipase A2 activity, EPC-K1, on spatial learning deficit and neuronal damage following transient cerebral ischemia was evaluated. Global ischemia was induced by four-vessel occlusion (4VO) for 20 min in rats. EPC-K1 (10 mg/kg IP) was administered either a) 15 min before induction of ischemia, b) immediately after, or c) 30 min after onset of reperfusion. One week after surgery spatial learning was tested in the Morris water maze. EPC-K1 reduced the deficit in spatial learning when given immediately or 30 min after the onset of reperfusion but not when applied 15 min before ischemia. Neuronal damage in the CA1 sector of the hippocampus produced by 4VO was slightly, but not significantly attenuated by posttreatment. The present data demonstrate that posttreatment with EPC-K1 exerts a protective effect on deficits in spatial learning induced by 4VO. These results support the hypothesis that lipid peroxidation and activation of phospholipase A2 contribute to functional alterations of the brain during reperfusion following forebrain ischemia.
 ...
PMID:Posttreatment with EPC-K1, an inhibitor of lipid peroxidation and of phospholipase A2 activity, reduces functional deficits after global ischemia in rats. 769 79

Maintenance of cerebral perfusion pressure is a prerequisite for the prevention of cerebral ischemia. Physiological fluctuations in systemic perfusion pressure are compensated by cerebrovascular autoregulation. Cerebral hypoperfusion could result from (1) systemic hemodynamic failure (eg, distal to severe arterial stenosis), overcharging the vasoregulatory capacity; (2) dysfunction and exhaustion of cerebrovascular autoregulation; or (3) both. Ultrasound offers an excellent temporal resolution, is noninvasive, and is easily applicable for follow-up investigations. Despite its poor spatial resolution, transcranial Doppler sonography has been used for determination of cerebral perfusion reserve studies measuring cerebral blood flow velocity (CBFV) during hypercapnia or application of vasoactive agents (eg, acetazolamide). This approach evaluates vasomotor regulation in patients with hemodynamic compromise distal to severe stenosis or occlusion of the brain supplying arteries. Monitoring CBFV during tilt table examinations directly measures cerebral autoregulation. In patients with systemic orthostatic hypotension, maintainance or failure of cerebrovascular compensation and, even more importantly, cerebrovascular dysautoregulation, despite normal systemic blood pressure regulation, may be demonstrated. Vasoneuronal coupling is reflected by CBFV variations during appropriate neuronal stimulation. Neuronal dysfunction is associated with CBFV abnormalities as exemplified by preconditions of focal cerebral dysfunction in the posterior cerebral artery (PCA) in migraineurs with aura, where massive alteration of vasoneuronal coupling and ischemia is threatening during spreading depression. A highly significant asymmetric gain of vasoneuronal coupling in the interictal state may act as a trigger mechanism in these patients. Testing for vasoneuronal coupling within the middle cerebral artery (MCA) territory is more difficult due to the poor spatial resolution with various neuronal stimuli (eg, motorsensory or cognitive paradigms), only eliciting local neuronal areas underrepresented in the MCA CBFV global changes. However, motor stimulation evoked CBFV may be used to indicate dysintegration of vasoneuronal coupling in the course of acute cerebral ischemia with sensorimotor hemiparesis and, moreover, seems to be of prognostic value regarding the motor deficit.
 ...
PMID:Cerebrovascular regulation and vasoneuronal coupling. 769

Neuronal and glial changes following experimental cerebral ischaemia showed neuronal shrinkage and astrocytic proliferation after temporary bilateral clamping of carotid arteries, and extensive neuronal damage with areas of haemorrhage following bilateral carotid ligations in rats.
 ...
PMID:Anoxic changes in cerebral cortex of albino rats following experimental carotid occlusion. 781 46

We have examined the effects of transient cerebral ischemia on performance of a one-trial passive avoidance task by chicks. Transient forebrain ischemia was induced by bilateral carotid artery occlusion for a period of 10 min. In one experimental group, ischemia was produced prior to training on the avoidance task whereas in the other group ischemic intervention was not made until 3 h after initial training. Sham-operated groups were matched to each of the experimental groups. All four groups were tested for retention of the avoidance response 24 h post-surgery. The sham-operated birds and those receiving post-training ischemia showed good retention of the avoidance response, whereas in birds which received ischemia prior to training there was significant amnesia. Neuronal damage, determined qualitatively using a silver impregnation method, was observed in several forebrain regions including the hippocampus, hyperstriatal regions, paleostriatum primitivum, ventral archistriatum, and lateral corticoid area. Damage was also observed in the Purkinje cells of the cerebellum. The behavioural and anatomical effects of transient forebrain ischemia have not been previously investigated in an avian species and the finding of significant amnesia for a learning task following ischemia is in good agreement with several behavioural studies in mammals.
 ...
PMID:Transient cerebral ischemia disrupts performance on a one-trial passive avoidance task in the domestic chick and is associated with neuronal degeneration in the central nervous system. 783 91

With use of iron histochemistry and immunohistochemistry, regional changes in the appearance of iron, ferritin, transferrin, glial fibrillary acidic protein-positive astrocytes, and activated microglia were examined from 1 to 24 weeks after transient forebrain ischemia (four-vessel occlusion model) in rat brain. Expression of the C3bi receptor and the major histocompatibility complex class II antigen was used to identify microglia. Neuronal death was confirmed by hematoxylin-eosin staining only in pyramidal cells of the hippocampal CA1 region, which is known as the area most vulnerable to ischemia. Perls' reaction with 3,3'-diaminobenzidine intensification revealed iron deposits in the CA1 region after week 4, which gradually increased and formed clusters by week 24. Iron also deposited in layers III-V of the parietal cortex after week 8 and gradually built up as granular deposits in the cytoplasm of pyramidal cells in frontocortical layer V. An increasing astroglial reaction and the appearance of ferritin-immunopositive microglia paralleled the iron accumulation in the hippocampal CA1 region, indicating that iron deposition was probably produced in the process of gliosis. Neither neuronal death nor atrophy was found in the cerebral cortex. Nevertheless, an astroglial and ferritin-immunopositive microglial reaction became evident at week 8 in the parietal cortex. On the other hand, the granular iron deposition in the pyramidal neurons of frontocortical layer V was not accompanied by any glial reaction in the chronic stage of ischemia. Three different types of iron deposition in the chronic phase after transient forebrain ischemia were shown in this study. In view of the neuronal damage caused by iron-catalyzed free radical formation, the late-onset iron deposition may be relevant to the pathogenesis of the chronic brain dysfunction seen at a late stage after cerebral ischemia.
 ...
PMID:Regional differences in late-onset iron deposition, ferritin, transferrin, astrocyte proliferation, and microglial activation after transient forebrain ischemia in rat brain. 786 Jun 55

During cerebral ischemia, accumulation of the glycolytic end product lactic acid may contribute to brain infarction. In vitro, lactic acid evokes a process of slowly evolving neuronal death characterized by a transient maintenance of cellular viability after initial injury. We examined effects of lactic acid on intracellular Ca2+ (Cai2+). Cultured neurons loaded with the fluorescent Ca2+ indicator fura 2 showed a marked increase in Cai2+ to as high as 600 nM. This increase occurred after lactic acid exposure when intracellular pH had normalized. Membrane potential was unaltered during this period, indicating that the Cai2+ increment was not a result of membrane depolarization. Increase in Ca2+ was prevented by incubating cultures in Ca(2+)-free solutions or exposing them to the L-type Ca2+ channel antagonist nimodipine. Cai2+ returned to resting levels within 20 min and remained normal during the remainder of the 4-h observation period. Neuronal Ca2+ homeostasis was disrupted after lethal exposure to lactic acid, in that subsequent exposure to 50 mM K+ failed to increase neuronal Cai2+. Cai2+ increment was integrated over a 20-min period to obtain a measure of neuronal Cai2+ load. This "calcium integral" was found to correlate directly with severity of neuronal damage observed 24 h later. Thus the Cai2+ increase integrated over time closely reflected the likelihood of lethal neuronal injury after lactic acid exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Intracellular Ca2+ transients evoked by lactic acid in cultured mammalian neurons. 786 48

Neuronal injury following focal cerebral ischemia is widely attributed to the excitotoxic effects of glutamate. However, critical analysis of published data on glutamate toxicity in vitro and the comparison of these data with in vivo release of glutamate and the therapeutic effect of glutamate antagonists raises doubts about a neurotoxic mechanism. An alternative explanation for glutamate-mediated injury is hypoxia due to peri-infarct spreading depression-like depolarizations. These depolarizations are triggered in the core of the ischemic infarct and spread at irregular intervals into the peri-infarct surrounding. In ischemically uncompromised tissue, the metabolic workload associated with spreading depression is coupled to an increase in blood flow and oxygen supply, assuring maintenance of oxidative respiration. In the penumbra region of focal ischemia, the hemodynamic constraints of collateral blood circulation prevail the adequate adjustment of oxygen delivery, leading to transient episodes of relative tissue hypoxia. The hypoxic episodes cause a suppression of protein synthesis, a gradual deterioration of energy metabolism and a progression of irreversibly damaged tissue into the penumbra zone. The generation of peri-infarct spreading depressions and the associated metabolic workload can be suppressed by NMDA and non-NMDA antagonists. As a result, the penumbral inhibition of protein synthesis and the progressing energy failure is also prevented, and the volume of ischemic infarct decreases. Interventions to improve ischemic resistance should therefore aim at improving the oxygen supply or reducing the metabolic workload in the penumbra region.
 ...
PMID:Glutamate-mediated injury in focal cerebral ischemia: the excitotoxin hypothesis revised. 791 80

Neuronal cell damage following ischaemia is postulated to be due to free radical induced lipid peroxidation, and ascorbic acid is supposedly an important non-enzymatic scavenger of such free radicals. This study was undertaken to evaluate the protective effect of ascorbic acid on the brain in a primate model after focal cerebral ischemia. Consumption of ascorbic acid in the monkey brain following ischaemia and its effect on macroscopic infarct size as demonstrated by 2, 3, 5, Triphenyl tetrazolium chloride (TTC) staining were used as parameters. The monkeys in the treated group were given 1 gram ascorbic acid parenterally every day for six days. The mean level of total ascorbic acid in right basal ganglia was 35.1 +/- 4.2 micrograms/mg of protein in the treated group as opposed to 22.9 +/- 2.1 micrograms/mg of protein in the nontreated group both before ischaemia. After right middle cerebral artery occlusion to produce focal cerebral ischaemia, the total ascorbic acid in the right basal ganglia 2 hours post ischaemia was 13.3 +/- 3.1 micrograms/mg of protein in the treated group as opposed to 9 +/- 1.6 micrograms/mg of protein in the untreated group. The average consumption of total ascorbic acid was 21.8 micrograms/mg of protein in the treated group and 13.9 micrograms/mg of protein in the nontreated group. Macroscopic infarct size as determined by TTC staining in the right cerebral hemisphere was 11.7 +/- 6.9 in treated group whereas it was 24.4 +/- 4.4 (expressed as percentage of right hemisphere) in the non-treated group. There was significant reduction in the size of the infarct in the treated group.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Ascorbic acid and focal cerebral ischaemia in a primate model. 821 84

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


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