Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Excessive extracellular fluid concentrations of the amino acids glutamate and aspartate play an important role in the pathogenesis of neuronal cell damage during hypoxia, hypoglycemia, and seizure. The purpose of these investigations was to test the hypothesis that bacterial meningitis causes progressive increase in excessive extracellular fluid concentrations of excitatory and inhibitory neurotransmitters. To test this hypothesis, Escherichia coli was injected intracisternally in juvenile rabbits after which neurotransmitter concentrations were measured with in vivo microdialysis. The data showed significant elevation of the excitatory amino acids aspartate and glutamate, as well as of the inhibitory neurotransmitters gamma-amino butyric acid and taurine in the excessive extracellular fluid of animals injected with E. coli compared with control animals injected with saline. However, concentrations of these excitatory and inhibitory amino acids rose late in the course of meningitis, at a time when the animals were hypotensive (mean blood pressure < or = 40 mm Hg). These data show that the major increase in excitatory neurotransmitters during experimental meningitis occurs in association with the cerebral ischemia produced by septic shock rather than being produced by the meningitis itself.
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PMID:Effect of experimental Escherichia coli meningitis on concentrations of excitatory and inhibitory amino acids in the rabbit brain: in vivo microdialysis study. 790 33

Activation of the gamma-amino butyric acid (GABA)-ergic system might protect against the damage that occurs after cerebral ischaemia. We examined this hypothesis by administering diazepam to rats subjected to transient middle cerebral artery occlusion (MCAO) using the intraluminal thread method. Diffusion MRI (DWI) and perfusion imaging (PI) were acquired during MCAO to assess brain tissue status and haemodynamics, respectively. Rats were intraperitoneally injected with either 10 mg kg(-1) diazepam (n = 5) or vehicle (n = 5) both 30 min and 90 min after the onset of MCAO. To exclude the possibility that neuroprotection was due to the hypothermic action of the drug, body temperature was maintained at 37-38 degrees C for up to 7 h postischaemia with a feed-back controlled thermoregulatory unit. Infarct volumes quantified 2 days after MCAO from T(2)-weighted images were similar in ischaemic control rats and in ischaemic rats treated with diazepam. We conclude that diazepam-induced enhancement of GABA(A) activity does not effectively protect against neuronal damage that occurs after transient MCAO in normothermic rats.
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PMID:Diazepam does not reduce infarct size in rats subjected to transient occlusion of the middle cerebral artery when normothermia is maintained. 1249 61

The neurobiologic mechanisms underlying the recovery process following stroke are poorly understood. The present study investigated glutamatergic and gamma-amino butyric acid (GABA)-ergic receptor densities following experimental stroke in rats exposed to different environmental housing or pharmacologic interventions. About 2 days after transient (120 min) middle cerebral artery (MCA) occlusion, the rats were singly housed in standard cages or were moved to an enriched environment and treated for 10 days with either 0.9% NaCl or with the alpha(2)-adrenoceptor antagonist, atipamezole (1.0 mg/kg, s.c.). The limb-placing, foot-slip, and water-maze tests were used to assess behavioral deficits and recovery following ischemia. The rats were decapitated on day 25 after the operation and their brains were processed for [3H]MK-801, [3H]D,L,-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), [3H]kainate, and [3H]muscimol autoradiography. Receptor binding site densities were different between sham-operated rats and ischemic rats only in the lesion core and lateral ventroposterior thalamic nucleus. Ischemic rats housed in an enriched environment and treated with atipamezole had better performance in the limb-placing test. The deficit in the water-maze test was most pronounced in ischemic rats housed in standard cages. There were a number of correlations between the behavioral data and receptor binding densities in ischemic rats. For example, recovery in the limb-placing test correlated with [3H]AMPA receptor binding sites in the contralateral frontal cortex (r=0.616, P<0.05), hindlimb cortex (r=0.649, P<0.05), and parietal cortex (r=0.674, P<0.05) in ischemic rats housed in an enriched environment. There were similar correlations between limb-placing recovery and [3H]kainate binding sites in the contralateral cortices in ischemic rats housed in standard cages. In addition, there were particularly strong clustered correlations between swimming speed in the water-maze test and [3H]AMPA receptor binding sites in the hippocampal subregions in the ischemic rats housed in an enriched environment. The present results suggest that transient focal cerebral ischemia does not induce significant long-term changes in glutamatergic and GABAergic receptors in areas remote from the infarct area. The correlational data, however, suggest an important role for the contralateral cortex in the behavioral outcome and maintenance of the recovered state of ischemic rats, depending on housing conditions. In addition, attenuation of spatial learning deficits observed in ischemic rats housed in an enriched environment might be due to an increase in the swimming speed through hippocampal AMPA receptor-mediated mechanisms.
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PMID:Behavioral deficits and recovery following transient focal cerebral ischemia in rats: glutamatergic and GABAergic receptor densities. 1252 49

This study investigated the changes in extracellular chemistry during reversible human cerebral ischaemia. Delayed analysis was performed on samples taken from a subgroup of patients during aneurysm surgery previously reported. Frozen microdialysis samples from 14 patients who had all undergone temporary clipping of the ipsilateral internal carotid artery (ICA) were analysed for another 15 amino acids with HPLC and for glycerol with CMA-600. Changes were characterised according to whether cerebral tissue oxygen pressure (PBO2) decreases were brief or prolonged. Brief ICA clipping (maximum duration of 16 minutes) in 11 patients was not associated with changes in amino acids or glycerol. Cerebral ischaemia, defined by a PBO2 decrease below 1.1 kPa for at least 30 minutes during ICA occlusion, occurred in 3 patients. None of whom developed an infarct in the monitored region. This prolonged reversible ischaemia was associated with transient delayed increases in gamma-amino butyric acid (GABA) as well as glutamate and glycerol, each by two-to-three folds. This study demonstrates detectable transient increases in human extracellular glutamate, GABA and glycerol during identified periods of reversible cerebral ischaemia, maximal 30-60 minutes after onset of ischaemia, but not in other amino acids detected by HPLC.
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PMID:Extracellular amino acid changes in patients during reversible cerebral ischaemia. 1646 26

In this study, we investigated whether the increase of inhibitory gamma-amino butyric acid (GABA) signal suppresses the excitatory glutamate signal induced by cerebral ischemia and the underlying mechanisms. In global cerebral ischemia, focal cerebral ischemia and oxygen-glucose deprivation, application of muscimol and baclofen, agonists of GABA(A) receptor and GABA(B) receptor, exerted neuroprotection. The agonists inhibited the increased assembly of the GluR6-PSD-95-MLK3 module induced by cerebral ischemia and the activation of the MLK3-MKK4/7-JNK3 cascade. Our results suggest that stimulation of the inhibitory GABA receptors can attenuate the excitatory JNK3 apoptotic signaling pathway via inhibiting the increased assembly of the GluR6-PSD-95-MLK3 signaling module in cerebral ischemia.
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PMID:Co-activation of GABA receptors inhibits the JNK3 apoptotic pathway via the disassembly of the GluR6-PSD95-MLK3 signaling module in cerebral ischemic-reperfusion. 1830 89

Bone marrow stromal cells (MSCs) are an excellent source of cells for treating a variety of central nervous system diseases. In this study, we report the efficient induction of committed neural progenitor cells from rat and human MSCs (NS-MSCs) by introduction of cells with the intracellular domain of Notch-1 followed by growth in the free-floating culture system. NS-MSCs successfully formed spheres, in which cells highly expressed the neural precursor cell markers. The commitment of spheres to neural lineage cells was confirmed by their successful differentiation into neuronal cells when exposed to a differentiation medium. To determine the therapeutic potential of NS-MSCs, cells were transplanted into the cortex and striatum in a rat model of focal cerebral ischemia. The survival, distribution, and integration of NS-MSCs in the host brain were very high, and at day 100, grafted NS-MSCs were positive for dopaminergic, glutamatergic, and gamma-amino butyric acid(GABA)ergic neuronal markers. They extended long neurites for nearly 6.3 mm and many of these expressed synaptophysin. Significant behavioral recovery was also observed in limb-placing and water-maze tests. These suggest a high potential for this MSC approach in the replenishment of neural cells for stroke and for a wide range of neurodegenerative conditions that require various types of neural cells.
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PMID:Committed neural progenitor cells derived from genetically modified bone marrow stromal cells ameliorate deficits in a rat model of stroke. 1943 12