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

Although neuronal death following brain ischemia was originally considered to be due to an energy deficiency resulting from an impaired respiratory chain, the observation of "delayed neuronal death" indicated some other factor. It is believed that delayed neuronal death after transient forebrain ischemia appears as a result of release of glutamate, an excitatory amino acid. In the present study, transient ischemia for 20 minutes in a rat four-vessel occlusion model was induced, and serial changes in histology and N-methyl-D-aspartate receptor (NMDA-R) binding were evaluated up to the chronic stage. Destruction of pyramidal cells and extensive astrocytic proliferation in the CA1 area of the hippocampus was completed by 10 days after cerebral ischemia followed by cerebral blood recirculation. However, the glutamate receptor subtype, NMDA-R, showed no change in all brain regions until after 10 days, but decreased in the hippocampus to 50% after 21 days despite no evidence of histological progression of neuronal death. The results show that the time course for appearance of light microscopic damage in the hippocampal region does not parallel that for depletion of NMDA-R binding sites.
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PMID:Loss of N-methyl-D-aspartate (NMDA) receptor binding in rat hippocampal areas at the chronic stage after transient forebrain ischemia: histological and NMDA receptor binding studies. 183 45

It has been proposed that lithium ion desensitizes neuronal receptors that function via the inositol phospholipid signaling mechanism. We examined the effects of lithium chloride on the morphologic outcome after 5 minutes of cerebral ischemia induced in gerbils by occluding both common carotid arteries under brief halothane anesthesia. In three treated groups of 10 gerbils each, 5 meq/kg i.p. lithium chloride was given 2 days, 1 day, and 2 hours before ischemia; 2 hours before ischemia; or immediately after the end of ischemia. Corresponding control groups of nine or 10 gerbils each received equivalent volumes of saline injected at comparable times. All gerbils were perfusion-fixed 1 week later, and neuronal density of the hippocampal CA1 pyramidal cells was determined. Lithium induced very mild intraischemic systemic hypothermia, but postischemic hyperthermia developed in both treated and control groups. Neuronal densities were equal in corresponding groups. The results indicate that our regimen of lithium administration provides no benefit in survival of hippocampal neurons, and intraischemic hypothermia of less than 0.8 degrees C is not protective. Other strategies to inactivate the signal transduction system that is specific for excitatory neurotransmission should be evaluated.
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PMID:Lithium ion does not protect brain against transient ischemia in gerbils. 184 49

Brief bilateral carotid artery ligation in adult spontaneously hypertensive rats (SHR) induced locomotor hyperactivity and lesions of the CA1 region of the hippocampus but had no effect in Wistar normotensive rats. This result suggests that high blood pressure amplifies the consequences of cerebral ischaemia. Treatment for 7 weeks with the calcium entry-blocker isradipine (5 mg/kg per day, subcutaneously) normalized blood pressure and attenuated the behavioural and histological consequences of cerebral ischaemia. Chronic treatment with hydralazine (25 mg/kg per day, subcutaneously) also normalized blood pressure but afforded no protection against the consequences of cerebral ischaemia. This suggests that the protective effect of antihypertensive treatment depends not only on the blood pressure-lowering action but may also be linked to the mechanism of action of the drug used.
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PMID:Protective effects of antihypertensive treatment with isradipine on the consequences of cerebral ischaemia in the spontaneously hypertensive rat. 184 26

Glutamate is an important factor in the mechanisms of neuronal damage following cerebral ischemia. Blockade of one type of glutamate receptor, the N-methyl-D-aspartate (NMDA) receptor, decreases brain infarct size in experimental models of permanent focal ischemia, but protection in models of transient reversible ischemia is ambiguous. We investigated the effect of the noncompetitive NMDA receptor antagonist dizocipiline (MK-801) on neuronal damage in the CA1 region of the rat hippocampus, using two models of reversible cerebral ischemia: 10 or 15 min of bilateral common carotid occlusion combined with hypotension, or 6-8.5 min of cardiac arrest. Histopathologic evaluation of neuronal damage was performed 7 days after the ischemic insults. Thirteen groups of rats (a total of 129 animals) were treated with saline or dizocilpine in single or multiple doses ranging from 0.1 to 5 mg.kg-1, given intravenously or intraperitoneally prior to and/or after the ischemic insult. In none of the dizocilpine-treated groups could neuronal protection be demonstrated in the CA1 region of the septal as well as dorsotemporal hippocampus, compared to a corresponding saline-treated group. We conclude that systemically administered noncompetitive NMDA receptor antagonists do not provide a marked protection against neuronal damage after a transient period of severe forebrain ischemia.
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PMID:Lack of protection by the N-methyl-D-aspartate receptor blocker dizocilpine (MK-801) after transient severe cerebral ischemia in the rat. 185 15

Calcium ion functions widely as an intracellular messenger and regulator. Intracellular calcium dyshomeostasis occurs during hypoxic/ischemic cell injury, and pharmacological antagonism of calcium entry into neurons has been considered to be of potential therapeutic value. Calcium antagonists, in addition, tend to improve cerebral perfusion of both the normal and abnormal (post-ischemic) brain. Studies of these agents have shown variable degrees of cerebroprotection in focal and global ischemia models. (S)-Emopamil is a phenylalkylamine-type calcium channel blocker which also exhibits stereoselective antagonism of the serotonin S2 receptor and has excellent blood-brain barrier penetrability. Protection of hippocampal CA1 neurons has been demonstrated with pre-ischemic administration of (S)-emopamil in global ischemia models. Our laboratory has compared the efficacy of pre- vs. post-ischemic (S)-emopamil treatment on neuronal necrosis resulting from 10 min of transient normothermic global ischemia in the rat. (S)-Emopamil pre-treatment, 20 mg/kg i.p., 30 min prior to ischemia, with a second dose 2.5 h later, resulted in 1.8-2.4 fold increases in numbers of surviving CA1 pyramidal neurons. Post-ischemic administration was ineffective. Intracerebral microdialysis has revealed a partial attenuation of dopamine release with pre-ischemic (S)-emopamil administration. In focal cerebral ischemia (middle cerebral artery occlusion in the rat), our laboratory has demonstrated a marked reduction in cortical infarct volume with (S)-emopamil pre- or post-treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium antagonists in the treatment of experimental cerebral ischemia. 185 3

Selective neuronal death in the CA1 sector of the hippocampus [delayed neuronal death (DND)] develops several days after transient global cerebral ischemia in rodents. Because NGF plays a potential role in neuronal survival, it was decided to study its effect in DND. We report here that intraventricular injection of NGF either before or after 5 min forebrain ischemia in the Mongolian gerbil significantly reduced the occurrence of DND. The tissue content of NGF in the hippocampus was decreased 2 d after ischemia and recovered to the preischemic level by 1 week. By the Golgi staining technique, changes first began in the dendrites of affected neurons as early as 3 hr. Such changes could be ameliorated by NGF treatment. Although previous knowledge of NGF is limited to the survival of cholinergic neurons in the CNS, it is assumed that other mechanisms must be operating in the hippocampus, for example, postsynaptic modification at dendrites or aberrant expression of NGF receptors possibly at the initial excitation period by glutamate. Furthermore, because previous work has shown that inhibition of protein synthesis reduces the occurrence of DND, a program leading to cell death might also be operating via de novo synthesis of certain protein(s), collectively termed "killer protein," because of a lack of NGF.
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PMID:Amelioration of delayed neuronal death in the hippocampus by nerve growth factor. 188 May 56

1. The brain cytoprotective effects of a putative calcium-associated protein kinase inhibitor, HA1077, as well as a calcium entry blocker nicardipine were evaluated in models of cerebral ischaemia in Mongolian gerbils. Morphological changes characterizing delayed neuronal death of selectively vulnerable CA1 pyramidal neurones in the hippocampus of the Mongolian gerbil brain occurred 7 days after transient bilateral occlusion of the common carotid arteries. 2. A single injection of HA1077 (1 and 3 mg kg-1, i.p.) 5 min after the occlusion led to a dose-dependent protection of the CA1 neurones. Repeated administrations of HA1077 (1 and 3 mg kg-1, i.p., twice daily for 7 days post-ischaemia) revealed an increase in the number of normal cells, compared to findings with a single administration. 3. In contrast to HA1077, nicardipine (0.3 and 1 mg kg-1, i.p.) did not reduce neuronal degeneration. 4. HA1077 did not interact with the ion channel within which MK-801 binds, as determined by receptor binding. 5. The calcium ionophore, A23187, caused a tonic contraction in canine cerebral arterial strips. HA1077, but not nicardipine, relaxed the A23187-induced contraction, concentration-dependently. 6. These results suggest that blockade of the intracellular actions of calcium may provide protection against ischaemic damage in the brain.
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PMID:Blockade of intracellular actions of calcium may protect against ischaemic damage to the gerbil brain. 191 80

We examined the characteristics of cerebral ischemia-induced behavioral deficit in the passive avoidance task and the effect of minaprine and other cytoprotective drugs on passive avoidance deficit induced by cerebral ischemia in Mongolian gerbils. Severe impairment of passive avoidance was apparent when the duration of the ischemia exceeded 2 min. Histopathological ischemic neuronal damage in CA1 neurons at 7 days after occlusion was also induced when the ischemia was over 2 min. Otherwise, although cerebral ischemia was carried out at 5 min, 2 hr, 5 hr or 24 hr after the training session, the passive avoidance deficit was produced 24 hr after the training session. When the training session was carried out 24 hr before the occlusion, minaprine, which was administered 30 min before the occlusion, led to a recovery of the response latency. Pentobarbital, diazepam and ethylapovincamine improved the passive avoidance deficit induced by 5-min bilateral carotid artery occlusion. On the other hand, the passive avoidance deficit was not ameliorated by Ca(++)-hopantenate, nicardipine and idebenone. The hippocampal damage at 7 days after occlusion was prevented by the drugs that ameliorated the passive avoidance deficit. The relationship between passive avoidance deficit and CA1 neuronal death in the hippocampus induced by cerebral ischemia warrants further attention.
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PMID:Effect of minaprine and other reference drugs on passive avoidance impairment induced by cerebral ischemia in Mongolian gerbils. 197 79

A quantitative autoradiographic study was made on the binding of the phosphatidylinositol system ligand [3H]inositol(1,4,5)-trisphosphate (IP3) to forebrain sections from rats decapitated various times after 10 min of forebrain ischemia. To investigate the effect of a deafferentation of the hippocampal CA1, kainic acid-induced CA3-lesioned rats with or without 10 min of cerebral ischemia, were also included. The highest binding was found in the hippocampal CA1. Ten min of cerebral ischemia did not change the binding significantly. Between 5 min and 1 h of recirculation there was a 25-35% binding decline in all regions. In the CA1, where the pyramidal cells became necrotic 6 days after ischemia, there was a further decline to 16% of control. In the cortex, where there is no necrosis in this model, binding did not return to control values until day 14. Four days after a selective CA3 lesion with kainic acid, there was a significant 25% decline in the cortex, dentate gyrus and CA1, whereas in the necrotic CA3 binding declined to 54% of control. Ten min of ischemia did not alter this binding significantly. This decrease in calcium mobilizing intracellular receptors after ischemia and seizures could be due to increased membrane degradation, or to a more specific down-regulation following increased intracellular concentration of calcium and IP3.
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PMID:Modification of [3H]inositoltrisphosphate binding in kainic acid-lesioned and postischemic rat hippocampus. 201 67

The effect of transient cerebral ischemia and intraventricular injection of kainic acid on adenylate cyclase and protein kinase C as labeled by [3H]forskolin ([3H]FOR) and [3H]phorboldibutyrate ester ([3H]PDBU) in several rat brain microregions was investigated in a quantitative autoradiographic study. Four days after transient four vessel occlusion a 80% loss of [3H]FOR and a 35% loss of [3H]PDBU binding could be measured in the CA1 stratum radiatum of operated Wistar rats as compared to control rats. Four days after intraventricular injection of kainic acid only a marginal loss of [3H]FOR and a 30% increase of [3H]PDBU binding was seen in the CA1 stratum radiatum while in the CA3 stratum lucidum and radiatum respectively a 30% loss of [3H]FOR and no significant change in [3H]PDBU binding was observed. As transient cerebral ischemia and intraventricular kainic acid injection are depleting the hippocampal CA1 region of CA1 pyramidal cells and axons of CA3 pyramidal cells respectively in rat brain, these findings strongly suggest that both adenylate cyclase and protein kinase C are localized in CA1 pyramidal cells of rat hippocampus.
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PMID:Post- and presynaptic lesions in the CA1 region of hippocampus: effect on [3H]forskolin and [3H]phorboldibutyrate ester binding. 203 10


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