Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stroke produces neuronal death by two general processes which differ in their temporal course. Acute neuronal death occurs within minutes, while delayed neuronal death evolves within 24 h. To better examine mechanisms of delayed death, we developed a new in vitro model of delayed neuronal injury using extended electrophysiological recordings in paired hippocampal slices. We exposed one hippocampal slice of each pair to 10 microM N-methyl-D-aspartate (NMDA) until the orthodromic CA1 PS disappeared. Thereafter, NMDA-treated slices regained near full recovery of PS amplitude within one hour. However, 10 h later, NMDA-treated slices demonstrated a rapid decline in PS amplitude of 82% +/- 15. CA1 orthodromic evoked PS was lost completely at an average 12.4 +/- 1.6 h after NMDA exposure. This sudden loss of response contrasted with paired, untreated slices, where CA1 PS could be elicited for 22.6 +/- 4.0 h (P < 0.05). Treatment with 10 mM MgCl2 begun after NMDA exposure and continued for 35 min, prevented delayed loss of CA1 orthodromic PS, which then could be elicited for 20.3 +/- 2.1 h. These results indicate that delayed injury can be evaluated using the hippocampal slice. They also suggest that activation of NMDA receptors can induce delayed neuronal injury in CA1 neurons, and that magnesium treatment after NMDA can prevent this injury.
 ...
PMID:Delayed neuronal injury induced by sub-lethal NMDA exposure in the hippocampal slice. 777 97

The protective effects of a novel dihydropyridine calcium antagonist with platelet-activating factor-antagonistic action, F-0401, on ischemic brain damage were investigated using experimental ischemia models in rats and gerbils. F-0401 (1 and 10 mg/kg, i.p.) prevented increases in water content, determined by the wet-dry method, in ischemic areas 24 hr after 1 hr of middle cerebral artery occlusion in the rat. Pretreatment with F-0401 (1 and 10 mg/kg, i.p.) prevented extravasation of Evans blue dye in the brain following 2 hr of bilateral carotid artery occlusion and 2 hr of reperfusion in the rat. Pretreatment with F-0401 (1 and 10 mg/kg, i.p.) protected against neuronal damage to hippocampal CA1 pyramidal cells following 3 and 5 min of forebrain ischemia in the gerbil. Immunostaining against microtubule-associated protein-2 also demonstrated preservation of CA1 neurons in F-0401-treated animals. Thus, this study shows that F-0401 prevents the occurrence of brain edema, disruption of blood-brain barrier and neuronal damage caused by cerebral ischemia. The results demonstrate that F-0401 may be a powerful candidate as a therapeutic agent in the treatment of acute stroke in man.
 ...
PMID:Protective effects of a novel calcium antagonist with platelet-activating factor-antagonistic action, F-0401, against ischemic brain damage. 784 11

Quantal analysis has provided evidence for a presynaptic contribution to long-term potentiation in hippocampal CA1 cells. This however leaves unexplained the observation that long-term potentiation has little or no effect on the NMDA receptor-mediated component of the synaptic signal. Here, I report that, in baseline conditions, the coefficient of variation of the AMPA/kainate receptor-mediated signal (CVA/K) is consistently larger than that of the NMDA component (CVNMDA), a result which can be explained if AMPA/kainate receptors are absent or nonfunctional at a proportion of synapses. Long-term potentiation is associated with a reduction in CVA/K, but no change in either the average amplitude of the NMDA component or CVNMDA. This is consistent with the proposal that long-term potentiation induction uncovers clusters of latent AMPA/kainate receptors, with no change in transmitter release.
 ...
PMID:Amplitude fluctuations of dual-component EPSCs in hippocampal pyramidal cells: implications for long-term potentiation. 791 Apr 67

Endothelin-1 (ET-1) is a potent cerebrovascular constrictor that has been implicated in brain ischemia. Utilizing the ETA receptor antagonist, BQ-123, the role of ET-1 in ischemic neuronal death following global ischemia was studied. BQ-123, administered ICV, either before and after ischemia or only after ischemia, increased hippocampal CA1 neuron survival in gerbils subjected to transient global ischemia. This study suggests that ETA receptor antagonists might be useful in neuronal salvage following stroke.
 ...
PMID:Peptidic endothelin-1 receptor antagonist, BQ-123, and neuroprotection. 793 21

Global ischemia, in the gerbil, produces profound hippocampal CA1 loss which leads to functional abnormalities (e.g. habituation impairment). In experiment 1, gerbils were subjected to 3 or 5 min of normothermic (brain) ischemia. Hypothermic groups were cooled to 32 degrees C for 12 h beginning 1 h after ischemia, while control groups (no hypothermia) regulated their own temperature. Exploration in a novel open field was assessed on days 3, 7 and 10 following ischemia and CA1 neurons were counted after 10- or 30-day survival. Both ischemia durations produced severe CA1 necrosis which resulted in increased open field activity. Hypothermia attenuated this behavioral pattern and substantially reduced CA1 necrosis against 3 min of ischemia when assessed at 10 and 30 days, but was only partially effective against a 5 min occlusion where, in addition, some cell death appeared to be delayed rather than prevented. In experiment 2, gerbils were occluded for 5 min and survived for 30 days. Twenty-four hours of hypothermia initiated 1 h after ischemia resulted in near total preservation of CA1 neurons. Thus, increasing the duration of post-ischemic hypothermia from 12 to 24 h produced much greater neuroprotection against severe ischemia. Prolonged post-ischemic hypothermia may be a valuable intervention in stroke patients.
 ...
PMID:Delayed and prolonged post-ischemic hypothermia is neuroprotective in the gerbil. 798 76

The adenosine A2 receptor antagonist CGS 15943 (0.1 mg/kg, i.p.) was tested for cerebroprotective activity in a gerbil stroke model. CGS 15943 markedly reduced stroke injury assessed by locomotor activity monitoring and by histopathological measurement of hippocampal CA1 pyramidal cell injury. It is proposed that a previously demonstrated reduction in the ischemia/reperfusion-evoked release of excitotoxic amino acids following CGS 15943 administration could account for its cerebroprotective actions.
 ...
PMID:CGS 15943, an adenosine A2 receptor antagonist, reduces cerebral ischemic injury in the Mongolian gerbil. 800 57

Vulnerability of CA1 pyramidal neurons to hypoxic and hypoglycemic insult was compared in hippocampal slices between the stroke-prone spontaneously hypertensive rat (SHRSP) and its mother strain, Wistar Kyoto rat (WKY). Stimulation of Schaffer collateral-commissural fibers induced D-2-amino-5-phosphonovalerate sensitive multi-component population spikes in slices from both strains when the external K+ concentration was elevated. The K+ concentration required for this phenomenon was significantly lower in SHRSP slice preparations than in those from WKY. The hypoxic and hypoglycemic insult in slice preparations is assumed to be equivalent to ischemic conditions in vivo. Although the short-term 'ischemic' insult caused a complete loss of population spikes in slices from both strains, a transient hyperexcitability, spreading depression-like depolarization, accumulation of extracellular K+ and reduction of extracellular Ca2+ occurred in SHRSP slices, but not in WKY. Time required for partial recovery of the population spike following the 'ischemic' insult was markedly increased in SHRSP slices compared with WKY. Thus, CA1 pyramidal neurons of SHRSP were more vulnerable to 'ischemic' insult than those of WKY. This vulnerability of pyramidal neurons in the SHRSP strain was independent of its hypertensive phenotype. A novel L-type Ca2+ channel blocker, S-312-d, its stereoisomer, S-312-1, and nimodipine protected the 'ischemic' insult-induced neuronal dysfunction at submicromolar concentrations. It is concluded that hippocampal neurons in SHRSP are innately vulnerable. This vulnerability is suggested to be due, at least in part, to some abnormality in K+ channel channels of hippocampal neurons.
 ...
PMID:Vulnerability of CA1 neurons in SHRSP hippocampal slices to ischemia, and its protection by Ca2+ channel blockers. 803 75

The effect of chronic administration of selective adenosine A1 receptor agonists and antagonists on the outcome of cerebral ischemia is entirely unknown. Therefore, we have investigated the impact of such regimens on the hippocampal adenosine A1 receptor density, and on the recovery from 10 min forebrain ischemia in gerbils. While acutely administered N6-cyclopentyladenosine (CPA) given at 0.02 mg/kg resulted only in a significant reduction of mortality, at 1 mg/kg it improved both survival and neuronal preservation in the hippocampal CA1 region. Acute treatment with 1,3-dipropyl-8-cyclopentylxanthine (CPX) significantly worsened the outcome and enhanced neuronal destruction. The effects of chronic administration of these drugs (15 days followed by 1 drug-free day) were opposite. Thus, although chronic CPA at 0.02 mg/kg did not have any effect at all, at 1 mg/kg both survival and neuronal preservation were significantly poorer than in controls, while chronic CPX resulted in a significant improvement of both measures. These results were not accompanied by adenosine A1 receptor up- or downregulation. Our study indicates that highly selective adenosine analogues may have therapeutic potential in treatment of cerebral ischemia/stroke and possibly other neurodegenerative disorders as well.
 ...
PMID:Chronic administration of selective adenosine A1 receptor agonist or antagonist in cerebral ischemia. 805 Apr 67

We examined endothelin (ET) receptors in the hippocampus CA1 subfields of stroke-prone spontaneously hypertensive rats subjected to a 10-min bilateral carotid occlusion and reperfusion. When delayed neuronal death had occurred in the pyramidal cell layer at 7 days after transient forebrain ischemia, the quantitative receptor autoradiographic method we used revealed a dramatic increase in number of 125I-ET-1 binding sites in the hippocampus CA1 subfields. The highest number of de novo binding sites appeared in the area corresponding anatomically to the pyramidal cell layer with neuronal death. These binding sites were characteristically the ETB receptor. The de novo 125I-ET-1 binding was mainly present on microglia aggregating with a high density in the damaged pyramidal cell layer. As ET-1- and ET-3-like immunoreactivities were highly expressed within astrocytes in damaged neural tissue, the possibility that microglia with the ETB receptor are activated to participate in the pathophysiology of ischemia-related neural tissue damage by astrocytic ET-1 and ET-3 produced in response to transient forebrain ischemia would have to be considered.
 ...
PMID:Microglia with an endothelin ETB receptor aggregate in rat hippocampus CA1 subfields following transient forebrain ischemia. 805 45

Calcium influx is believed to play a critical role in the cascade of biochemical events leading to neuronal cell death in a variety of pathological settings, including cerebral ischemia. The synthetic omega-conotoxin peptide SNX-111, which selectively blocks depolarization-induced calcium fluxes through neuronal N-type voltage-sensitive calcium channels, protected the pyramidal neurons in the CA1 subfield of the hippocampus from damage caused by transient forebrain ischemia in the rat model of four-vessel occlusion. SNX-111 provided neuroprotection when a single bolus injection was administered intravenously up to 24 hr after the ischemic insult. These results suggest that the window of opportunity for therapeutic intervention after cerebral ischemia may be much longer than previously thought and point to the potential use of omega-conopeptides and their derivatives in the prevention or reduction of neuronal damage resulting from ischemic episodes due to cardiac arrest, head trauma, or stroke. Microdialysis studies showed that SNX-111 was 3 orders of magnitude less potent in blocking potassium-induced glutamate release in the hippocampus than the conopeptide SNX-230, which, in contrast to SNX-111, failed to show any efficacy in the four-vessel occlusion model of ischemia. These results imply that the ability of a conopeptide to block excitatory amino acid release does not correlate with its neuroprotective efficacy.
 ...
PMID:A selective N-type calcium channel antagonist protects against neuronal loss after global cerebral ischemia. 810 3


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