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

The Mongolian gerbil was used as a model of aging because of its relatively short lifespan, genetic homogeneity and the fact that data had been collected previously. Furthermore, gerbils have been widely used in biomedical investigations of stroke and epilepsy. Age-related differences in signal transmission and transduction systems were investigated in brains of three-, 11- and 21-month-old gerbils by morphological and in vitro receptor autoradiographic studies. Morphometric analysis revealed a decreased number of neurons in layer III of the occipital cortex and also a decrease in cerebellar Purkinje cells in 21-month-old animals. However, no statistical differences were observed in the hippocampal formation, the dorsolateral striatum and layer III of the frontal cortex. Autoradiography was used to map muscarinic cholinergic (labeled with [3H]quinuclidinyl benzilate), serotonin2 ([3H]spiperone), dopamine D2 ([3H]spiperone), adenosine A1 ([3H]cyclohexyladenosine), GABAA ([3H]muscimol), naloxone ([3H]naloxone), protein kinase C ([3H]phorbol 12,13-dibutyrate), adenylate cyclase ([3H]forskolin), cyclic AMP ([3H]cyclic AMP) and L-type Ca2+ channels ([3H]PN200-110). Muscarinic cholinergic receptor and protein kinase C, cyclic AMP and L-type Ca2+ channels were significantly decreased in the cerebral cortex and/or in the CA1 subfield of the hippocampus in the 21-month-old group. Muscarinic cholinergic receptor and L-type Ca2+ channel binding sites were significantly reduced in the dentate gyrus. In contrast, protein kinase C was increased in this area in the 21-month-old group. Also, naloxone binding sites were increased in the CA3 subfield, hilus, dentate gyrus and molecular layer of the cerebellum in the 11- and 21-month-old groups. Muscarinic cholinergic, serotonin2 and dopamine D2 receptors and adenylate cyclase were significantly decreased in the striatum. On the other hand, adenosine A1 and GABAA receptors remained unchanged in the 21-month-old group. Although age-related histopathological abnormalities were only observed in the occipital cortex and in the cerebellum, alterations of signal transmission and transduction systems were noticed in all areas examined (e.g. cerebral cortex, CA1 subfield, dentate gyrus and striatum). These data indicate that changes in these receptors and binding sites may be related to dysfunction of learning and memory and to the loss of motor function. The aged gerbil model is a good system for studying aging and is of value for simulating aging after epilepsy and stroke.
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PMID:Effects of aging on signal transmission and transduction systems in the gerbil brain: morphological and autoradiographic study. 134 8

We examined the ability of phenyl-t-butyl-nitrone (PBN), an electron spin trapper, to attenuate ischemia-induced forebrain edema and hippocampal CA1 neuronal loss in gerbils, and to protect rat cerebellar neurons in primary culture from glutamate-induced toxicity. PBN, given i.p. at 75 or 150 mg/kg 30 min before ischemia (5 min occlusion), increased survival (at 7 days) of CA1 neurons from 60 +/- 14 (vehicle-treated, n = 17) to 95 +/- 15 (P less than 0.05, n = 15) and 145 +/- 3 (P less than 0.01, n = 15), respectively. When gerbils were treated with PBN (50 mg/kg, i.p.) immediately and 6 h after reperfusion, followed by b.i.d. for an additional 2 days, CA1 neurons survival improved from 35 +/- 9 (vehicle, n = 20, 6 min occlusion) to 106 +/- 17 (P less than 0.01, n = 13). In gerbils exposed to a more severe ischemia (10 min), pretreatment with 150 mg/kg PBN increased the survival of CA1 neurons from 6 +/- 6 (vehicle) to 27 +/- 10 (P less than 0.05, n = 11). Pretreatment with PBN, at 150 mg/kg, reduced forebrain edema (following 15 min ischemia) by 24.7% (P less than 0.01, n = 16). PBN at 50 mg/kg, i.p. had no hypothermic effect and at 75 or 150 mg/kg caused a transient hypothermia. The presence of PBN in the brain was confirmed in microdialysis samples and brain tissue extract using HPLC. In vitro, PBN protected rat cerebellar neurons against 100 microM glutamate-induced toxicity with an EC50 value of 2.7 mM. Our results further support the concept that free radicals contribute to brain injury following ischemia and suggest the potential therapeutic application of electron spin trappers in stroke.
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PMID:Neuroprotective effects of phenyl-t-butyl-nitrone in gerbil global brain ischemia and in cultured rat cerebellar neurons. 135 99

To investigate the role of glutamate release in cerebral ischemia, the amounts of amino acids (glutamate, taurine, alanine, glycine and glutamine) released in the hippocampal CA1 region of stroke-prone SHR (SHRSP), stroke-resistant SHR (SHRSR) and normotensive rats (WKY) were determined during and after cerebral ischemia by the microdialysis method under halothane anesthesia. Cerebral ischemia was produced by the occlusion of both common carotid arteries for 20 min. The basal amino acids release did not differ among the three strains of rats, but ischemic glutamate and taurine releases were more marked in SHRSP than in other strains. These results suggest that the massive glutamate release during cerebral ischemia of SHRSP might be related with severe neuronal cell injury.
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PMID:Changes in extracellular concentration of amino acids in the hippocampus during cerebral ischemia in stroke-prone SHR, stroke-resistant SHR and normotensive rats. 162 92

The ability of diphenylhydantoin (DPH) to protect against hypoxia-induced neuronal damage was examined using electrophysiological recordings of extracellular evoked potentials from CA1 pyramidal neurons of rat hippocampal slices in vitro. In normal medium, a 15-min hypoxic insult (95% N2/5% CO2) produced rapid and complete loss of Schaffer collateral synaptic transmission, which only recovered to 20% of pre-hypoxia values after 90 min of reoxygenation. DPH (20 microM) bath applied prior to onset of hypoxia slowed the loss of transmission during hypoxia, and led to 75% recovery of evoked potentials upon reoxygenation. Thus, DPH appears to protect against hypoxia-induced loss of synaptic transmission, and may thereby lessen neuronal damage and cognitive dysfunction associated with stroke.
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PMID:Diphenylhydantoin protects against hypoxia-induced impairment of hippocampal synaptic transmission. 164 90

1. The effect of chlormethiazole, and other drugs which potentiate gamma-aminobutyric acid (GABA) function on delayed neuronal death in the hippocampus has been examined in the gerbil. 2. Chlormethiazole (100 mg kg-1, i.p.) and two other drugs previously reported to be neuroprotective (dizocilpine, 3 mg kg-1, i.p. and ifenprodil, 4 mg kg-1, i.p.) were all found to prevent neurodegeneration of CA1/CA2 neurones in the hippocampus when given 30 min before a 5 min episode of bilateral carotid artery occlusion. 3. Chlormethiazole (100 mg kg-1) was neuroprotective when given up to 3 h, after the ischaemic episode. 4. Given 1 h after the cartoid artery occlusion, chlormethiazole produced significant protection against hippocampal neurodegeneration at a dose of 50 mg kg-1, but not at 25 mg kg-1. 5. Phenobarbitone (100 mg kg-1, i.p.) and Saffan (alphaxalone, 45 mg kg-1 plus alphadalone, 15 mg kg-1, i.p.) were not protective when given 1 h after the ischaemic episode while pentobarbitone (30 mg kg-1, i.p.) had a modest protective effect. 6. Evidence is presented to show that neither the operating procedure nor the chlormethiazole administration lowered rectal or cerebral temperature. 7. The data suggest that chlormethiazole may be a useful treatment in the prevention of neurodegeneration following stroke or cardiac arrest.
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PMID:Neuroprotective activity of chlormethiazole following transient forebrain ischaemia in the gerbil. 179 7

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.
Stroke 1991 Jan
PMID:Lithium ion does not protect brain against transient ischemia in gerbils. 184 49

Two groups of rats were tested on a variety of motor and cognitive tasks after either 10 minutes of two-vessel occlusion forebrain ischemia (n = 8) or sham operative procedures (n = 6). Histological injury was absent in the sham-operated group. In the ischemic group, hippocampal injury was restricted to field CA1, while damage in the neocortex and caudoputamen was sparse. Motor tests performed on postoperative days 18 and 28 revealed no significant differences between the ischemic and sham-operated groups. Retention performance of a radial maze discrimination task was impaired, with a significant but transient increase in both working and reference memory errors. Passive avoidance acquisition and retention were not significantly affected, although conclusions concerning the utility of this task must be reserved because of variability in the behavior of the sham-operated rats. Morris maze spatial navigation (place learning) and open-field activity were insensitive to treatment group. These functional results are consistent with the observed histological injury and what is known about hippocampal injury and behavior, and they provide further guidance for the development of neurological assays appropriate for discriminating outcome from forebrain ischemia in rats.
Stroke 1991 Aug
PMID:Forebrain ischemia induces selective behavioral impairments associated with hippocampal injury in rats. 186 51

Several feasible mechanisms have been proposed as sources of neuronal damage from ischemia and subsequent reperfusion. Included among these are oxidative damage caused by free radical production and lipid peroxidation and products derived from phospholipid breakdown. A series of 4-thiazolidinone compounds represented by LY178002 (5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene-4-thiazolidinon e) have been described as inhibitors of multiple enzymes in the arachidonic acid cascade, including fatty acid cyclooxygenase, 5-lipoxygenase, and phospholipase A2. Accordingly, we evaluated LY178002 in a four-vessel occlusion model of global forebrain ischemia with reperfusion. A 2-hour pretreatment of 11 male Wistar rats with 150 mg/kg LY178002 significantly protected against striatal (p = 0.0007) and hippocampal CA1 (p = 0.006) damage after 30 minutes of global ischemia. Similar protection was observed for the striatum (p = 0.005) and hippocampal CA1 layer (p = 0.025) after pretreatment of 13 rats with 50 mg/kg LY178002. We further evaluated LY178002 as a possible inhibitor of lipid peroxidation because part of its chemical structure incorporates the aromatic backbone of the known antioxidant butylated hydroxytoluene. We found LY178002 to be a potent inhibitor of iron-dependent lipid peroxidation. Few substances possessing a single pharmacological activity have been found to be of significant therapeutic benefit in global ischemia of 30 minutes' duration because the mechanisms that lead to cell death in response to ischemia are likely to be multifactorial. Thus, the efficacy of LY178002 in this model may be due to its ability to inhibit multiple sources of damage.
Stroke 1991 Aug
PMID:LY178002 reduces rat brain damage after transient global forebrain ischemia. 186 52

Leucocytes play an important role in inflammation and immunologic responses. They might be of special significance under pathophysiological conditions of the brain i.e. ischaemia or stroke. It has been shown that neutropenic animals undergoing reversible ischaemia show higher post-ischaemic blood flow, suggesting improved post-ischaemic perfusion. In this study it was investigated therefore, whether polymorphonuclear leucocytes contribute to the nerve cell loss in the hippocampus after a reversible period of ischaemia. Rats were made neutropenic with a specific anti-serum against rat polymorphonuclear leucocytes yielding leucocyte counts less than 10% of normal. The animals were then subjected to 15 min reversible forebrain ischaemia. Quantitative histology was performed after a survival period of 7 days. Nerve cell counts in the frontal cortex and in the CA1 and CA3 sectors of the hippocampus did not reveal any differences between neutropenic rats and animals with normal leucocyte counts. From the results it might be concluded that neutrophils do not significantly contribute to the selective post-ischaemic nerve cell damage in the rat.
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PMID:Leucocyte depletion does not affect post-ischaemic nerve cell damage in the rat. 192 25

The phencyclidine analogue [3H](1-[2-thienyl]cyclohexyl)piperidine (3H-TCP) binds to the ion channel associated with the N-methyl-D-aspartate receptor channel complex. In vitro autoradiography indicates that the distribution of 3H-TCP binding in brain closely parallels that of [3H]glutamate binding to the N-methyl-D-aspartate receptor. In nine 7-day-old rats, an acute focal hypoxic-ischemic insult produced by unilateral carotid artery ligation and subsequent exposure to 8% oxygen acutely reduced 3H-TCP binding ipsilateral to the ligation by 30% in the CA1, by 27% in the CA3, by 26% in the dentate gyrus, and by 17% in the striatum compared with values from the contralateral hemisphere. In 10 littermates that received 1 mg/kg of the neuroprotective noncompetitive N-methyl-D-aspartate antagonist MK-801 immediately before hypoxic exposure, the regional distribution of 3H-TCP binding in hypoxic-ischemic brain was relatively preserved and there were no interhemispheric asymmetries in 3H-TCP binding densities. In addition, in three unoperated rats decapitated 24 hours after MK-801 treatment, 3H-TCP binding was reduced by 15-35%; similar bilateral suppression of 3H-TCP binding was detected in MK-801-treated ligates. Our data indicate that 3H-TCP autoradiography can be used to assay the efficacy of neuroprotective agents in this experimental model of perinatal stroke.
Stroke 1990 Feb
PMID:Effects of hypoxia-ischemia and MK-801 treatment on the binding of a phencyclidine analogue in the developing rat brain. 196 95


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