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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of selective injury of hippocampal neurons on the consolidation of memory traces was studied in gerbils (meriones unguiculatus) after production of mild cerebral ischemia. The right carotid artery was permanently ligated, and animals without gross neurological deficits ("symptom-negative" gerbils) were selected. Eight days and eight weeks after vascular ligation, cell counts of hippocampal neurons were carried out and correlated with regional blood flow and the acquisition of operant behaviour. Eight days after carotid artery occlusion, learning behaviour was significantly impaired although the number of hippocampal neurons had not changed and blood flow had even increased above normal. After eight weeks, learning behaviour and blood flow were normal but now a significant loss of pyramidal neurons was present in the CA1 and CA2 sectors of the hippocampus. Our observations demonstrate that it is possible to detect subtle functional disturbances by appropriate behavioural investigation before manifestation of selective injury of the hippocampus. Recovery of integrative function, despite persistent cellular damage, provides further evidence for central nervous plasticity.
Stroke
PMID:Selective vulnerability of hippocampus and disturbances of memory storage after mild unilateral ischemia of gerbil brain. 381 Jul 15

The efficacy of nimodipine in preventing ischemic brain injury was tested in rats subjected to a 20-minute period of high-grade forebrain ischemia by 4-vessel occlusion. Three minutes after restoration of circulation to the brain, an intravenous bolus of 5 micrograms/kg nimodipine or an equivalent amount of vehicle or saline was given, followed by continuous intravenous infusion of the respective solution at 1 microgram/kg/min for 2 hours. In a second series, a larger bolus (20 micrograms/kg of nimodipine) and longer infusion period (6 hours) were employed. Histopathology of the brain was evaluated blindly 72 hours later and graded on a conventional 3-point scale. There was no significant effect of treatment in either series. In the 6-hour series, the percent of cerebral hemispheres showing damage of Grades 2 or 3 in zone CA1 of the hippocampus and in the striatum, respectively, was 100 and 40% for the nimodipine-treated rats, 100 and 42% for rats receiving vehicle, and 75 and 25% for animals receiving saline. Thus, this study revealed no beneficial effect of nimodipine when given following a 20-minute period of severe forebrain ischemia.
Stroke
PMID:Failure of nimodipine to prevent ischemic neuronal damage in rats. 381 Jul 55

The cytoprotective effects of MK-801 and NBQX, selective N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists, respectively, were compared both singularly and in combination in models of transient severe forebrain and transient focal cerebral ischemia. After 10 minutes of four-vessel occlusion ischemia, the sodium salt of NBQX (30 mg/kg IP) given at the time of reperfusion and, subsequently, 15 and 30 minutes later produced a dramatic reduction in CA1 hippocampal necrosis at 7 days. This effect was not obtained with the intraperitoneal administration of either MK-801 (1 mg/kg x 3) or the combination of both NBQX and MK-801 given at the same time intervals. This effect of intraperitoneal NBQX alone was reproduced in a two-vessel occlusion/hypotension model using this same drug administration. Delayed treatment with both NBQX and GYKI 52466, but neither MK-801 nor the combination of NBQX and MK-801 given after a delay, produced a significant reduction in the mean volume of neocortical infarction after transient focal ischemia. We conclude that the AMPA receptor may play a more important role than the NMDA receptor in both selective ischemic necrosis of hippocampal neurons and in neocortical infarction. AMPA antagonists should be subjected to clinical stroke trials.
Stroke 1993 Dec
PMID:AMPA antagonists: do they hold more promise for clinical stroke trials than NMDA antagonists? 750 38

The development of selective, systemically active alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate antagonists over the last 4 years has enabled the role of this excitatory amino acid receptor subtype to be scrutinised in the different models of ischaemia. The animal models of cerebral ischaemia can be subdivided into two major categories: focal ischaemia, in which the resulting infarct resembles the clinical condition of stroke; and models of severe forebrain ischaemia, in which there is delayed neuronal degeneration of hippocampal CA1 neurones. The neuropathology in the latter models resembles the clinical condition seen following a cardiac arrest, for example. It is well established that N-methyl-D-aspartate (NMDA) antagonists such as MK-801, 3-(2-carboxypiperazine-4-yl)-propenyl-1-phosphonate (CPPene), DL-(E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP 37849), and N-(1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine hydrochloride (CNS 1102) are neuroprotective in animal models of focal ischaemia. However, in models of severe forebrain ischaemia NMDA antagonists produced only partial protection. The discovery of 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX) as a systemically active AMPA receptor antagonist enabled the role of this receptor subtype in ischaemia to be investigated. NBQX was shown to be neuroprotective against delayed neuronal degeneration of hippocampal CA1 neurones in animal models of severe forebrain ischaemia. Recent studies have demonstrated that NBQX administration can be delayed by up to 12 h and amelioration of delayed neuronal degeneration of hippocampal CA1 neurones can still be seen. NBQX has also been shown to be neuroprotective in animal models of permanent and temporary middle cerebral artery occlusion. 1-(Aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466), a systemically active noncompetitive AMPA/kainate antagonist, was neuroprotective against focal ischaemia but was unable to attenuate hippocampal CA1 neuronal degeneration. Whilst the newer compounds such as (3SR,4aRS,6RS,8aRS)-6-[2-(1H-tetrazol-5-yl )-ethyl]-1,2,3,4,4a,5,6,7,8a-decahydroisoquinoline-3-carboxylic acid (LY 215490) and 6-(1-imidazolyl)-7-nitroquinoxaline-2,3(1H,4H)-dione (YM900) have been demonstrated to be neuroprotective in focal ischaemia models, there is still a lack of information with regard to their efficacy in models of severe forebrain ischaemia. It appears from initial studies that AMPA/kainate antagonists have a better behavioural profile than NMDA antagonists in terms of a lack of phychostimulant and phychotomimetic effects. However, these antagonists have their own problems in that they cause severe depression of glucose utilisation in the central nervous system at neuroprotective doses.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The pharmacology of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate antagonists and their role in cerebral ischaemia. 752 37

1. Cerebral ischemia of 5 min duration was induced in unanesthetized gerbils by bilateral occlusion of the carotid arteries. 2. The extent of cerebral damage was assessed by the elevation of motor activity in comparison with pre-ischemic levels and by a histological assessment of the extent of neuronal degeneration of the CA1 area of the hippocampus. 3. The GABA transport inhibitor CI-966 (10 mg/kg i.p.) was tested for cerebroprotective activity in a gerbil stroke model. CI-966 reduced the extent of stroke injury as assessed by locomotor activity and measurement of hippocampal CA1 pyramidal cell injury. 4. It is proposed that enhancement of extracellular GABA levels during ischemia accounts for the cerebroprotective actions of CI-966.
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PMID:CI-966, a GABA uptake inhibitor, antagonizes ischemia-induced neuronal degeneration in the gerbil. 755 51

2-Amino-N-(1,2-diphenylethyl)-acetamide hydrochloride (FPL 13950) has been demonstrated to have good anticonvulsant efficacy and a relative lack of acute side effects in rodents. Similar in structure to remacemide hydrochloride, it was also shown to possess weak potency as an uncompetitive antagonist of N-methyl-D-aspartic acid (NMDA) receptors. In our study FPL 13950 was profiled preclinically as a potential neuroprotective agent with respect to lengthening the survival time of rodents exposed to hypoxia, as well as for ability to protect the vulnerable CA1 pyramidal neurons of the rat and dog from the consequences of global ischemia. Under conditions of hypoxia, pretreatment of rodents with FPL 13950 resulted in an extension in the time to loss of the righting reflex (rats) and mortality (rats and mice). This occurred whether the rats were maintained at ambient body temperature or made hyperthermic. When administered after 30 min of four-vessel occlusion global ischemia for periods of either 7 (b.i.d.) or 14 days (s.i.d.), FPL 13950 exhibited protection of the vulnerable CA1 hippocampal neurons in rat. In the 14-day treatment study the CA3 neurons were evaluated and FPL 13950 was found to prevent the lesser degree of ischemic-induced damage to this hippocampal region. In ischemic rats treated with FPL 13950 for 7 days, electrophysiological responses of CA1 neurons (orthodromic and antidromic population spikes, in vitro) were also preserved after FPL 13950 treatment. FPL 13950 was administered i.v. at 30 min after 8 min of clamping the ascending aorta in dogs, followed by a b.i.d./s.i.d. dosing regimen for 1 wk. Neuronal damage to CA1 was considerable in the saline-treated ischemic animals but significantly protected in dogs receiving FPL 13950. FPL 13950 continues to serve as a potential backup candidate for remacemide HCl which is currently in clinical trials for patients with stroke and epilepsy.
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PMID:Neuroprotective actions of 2-amino-N-(1,2-diphenylethyl)-acetamide hydrochloride (FPL 13950) in animal models of hypoxia and global ischemia. 763 64

We examined the effect of cholecystokinin octapeptide sulfated type (CCK-8S) on dysfunction of CA1 pyramidal neurons induced by in vitro ischemic insult in hippocampal slices of stroke-prone spontaneously hypertensive rats (SHRSP). CCK-8S shortened the time required for partial recovery from block of a population spike produced by ischemia. Furthermore, CCK-8S reduced ischemic insult-induced accumulation of K+ in extracellular space. Suppression of the K+ conductance by the CCKB receptor activation is suggested to contribute to neuroprotection by CCK-8S.
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PMID:CCKB receptor activation protects CA1 neurons from ischemia-induced dysfunction in stroke-prone spontaneously hypertensive rats hippocampal slices. 765 2

We investigated the effect of beraprost sodium (BPS), a new prostacyclin analog, on behavioral and neuropathological changes induced by a 10-min occlusion of the left carotid artery in gerbils. Gerbils were treated orally with BPS (1-100 micrograms/kg) 30 min before occlusion. Pathological evaluation of neural damage in the CA1 region of the hippocampus was performed 7 d after the ischemic insults. In the symptomatic group, in which the stroke index score was > 10, symptomatic behaviors, such as head cocked, splayed out hind limb, circling, and various similar behaviors, were observed. Pathologically, almost all CA1 neurons were destroyed 7 d after ischemia in the symptomatic group. BPS improved the stroke index during ischemia and neuropathological changes 7 d later, with statistical significant improvement occurring at a dose of 100 micrograms/kg.
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PMID:Effect of beraprost sodium (BPS) on the postischemic neuropathological changes and stroke index after left carotid artery occlusion in gerbils. 770 4

The protective effect of nebracetam on ischemic neuronal damage was histologically examined in the pyramidal cell layer of the hippocampal CA1 subfield 7 days after operation using stroke-prone spontaneously hypertensive rats (SHRSP) subjected to 10-min bilateral carotid occlusion. Nebracetam (50 and 100 mg/kg), given orally 10 min after reperfusion, dose-dependently protected against ischemic delayed neuronal damage in the SHRSP with occlusion; however, the blood pressure remained unchanged following nebracetam administration. These findings further support the notion that nebracetam protects against ischemic delayed neuronal cell death in the hippocampus.
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PMID:Histological evidence for neuroprotective action of nebracetam on ischemic neuronal injury in the hippocampus of stroke-prone spontaneously hypertensive rats. 774 52

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


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