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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preischemic hyperglycemia worsens brain damage after ischemia, and characteristically leads to post-ischemic seizures and a pan-necrotic lesion in substantia nigra pars reticulata (SNPR). The excitatory input to SNPR could contribute to the damage observed. By performing a unilateral frontal cortex lesion 6-19 days prior to the ischemia, we wanted to explore whether a decrease in excitatory input to the ipsilateral SNPR ameliorate the seizures or alter the light microscopical damage in SNPR. Our results demonstrate that unilateral frontal cortex lesion did not alter the development of fatal post-ischemic seizures after 10 min of ischemia in hyperglycemic subjects. Thus, 7/8 animals developed seizures and died within 20 h of recovery. This study also failed to show any difference between the left and right side in post-ischemic SNPR damage after 15 h of recovery in animals with preischemic unilateral frontal cortex lesion. Furthermore, no side difference was observed in any other brain region evaluated. The results thus suggest that the pan-necrotic lesion in SNPR after hyperglycemic ischemia is not caused by excessive excitatory input from frontal cortex. A decrease in the GABA-ergic inhibitory input from caudoputamen to SNPR may be a more important mechanism for the ensuing excitotoxic post-ischemic SNPR damage, and for seizure development.
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PMID:Frontal cortex lesion prior to hyperglycemic ischemia: no decrease in ensuing substantia nigra pars reticulata damage or fatal post-ischemic seizures. 157 9

We have investigated the GABAergic system in rat hippocampus at 1 hour and up to 21 days following 20 min of global cerebral ischemia. Distribution of 3H-GABA (in excess of unlabeled baclofen) and 3H-Ro-15-1788 (benzodiazepine antagonist) binding sites in hippocampus was studied utilizing quantitative autoradiography. The 3H-GABA binding was unchanged (p greater than 0.01) after ischemia, whereas the 3H-Ro-15-1788 binding decreased significantly (p less than 0.01) in all hippocampal subfields 1-21 days after ischemia. Using microdialysis in CA1, we found that K(+)-stimulated GABA release at 1 hour and 1 day after ischemia was unchanged (p greater than 0.01) in comparison to preischemic controls. Electrophysiological recordings were made from CA1 of hippocampal slices prepared from rats sacrificed 1 hour, 1 day and 2 days after ischemia. Field potentials evoked by stimulation of the Schaffer collaterals showed no differences (p greater than 0.01) from those taken from controls. Postischemic intracellular recordings from the CA1 pyramidal cells showed that fast and slow inhibitory postsynaptic potentials were readily evoked on orthodromic stimulation. Together with our previous morphological results, demonstrating survival of hippocampal interneurons following ischemia, we conclude that hippocampal GABAergic interneurons preserve their inhibitory potential in the period preceding delayed CA1 pyramidal cell death. This conclusion taken together with the observation that postischemic 3H-Ro-15-1788 binding in hippocampus declined, suggest that benzodiazepines (by increasing the receptor affinity), GABA analogs, and GABA uptake inhibitors may be useful in the treatment of ischemic CA1 pyramidal cell death in the rat.
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PMID:Inhibition in postischemic rat hippocampus: GABA receptors, GABA release, and inhibitory postsynaptic potentials. 165 Jul 6

Increased excitation may be involved in the development of delayed CA1 pyramidal cell death in hippocampus after global cerebral ischemia. Therefore we investigated the possible neuroprotective effect of the GABA uptake inhibitor, R-(-)-1-(4,4-(3-methyl-2-thienyl)-3-butenyl)-3-piperidine carboxylic acid (No-328), in a rat cerebral ischemia model of delayed CA1 pyramidal cell death. No-328 in doses of 36 mg/kg given 30 min before, and 1, 24, 48 and 72 h after ischemia significantly reduced the CA1 neuron loss. Doses of 50 mg/kg of No-328 given immediately before, 24 h and 48 h after ischemia, also reduced the CA1 neuron loss significantly. Furthermore, we demonstrated that postischemic treatment with diazepam (4 x 15 mg/kg) significantly reduced the CA1 neuron loss. However, postischemic treatment with several doses (5 x 12 mg/kg) of the GABA analog, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), offered no CA1 neuron protection when given alone, but when administrated together with diazepam (4 x 15 mg/kg) it significantly reduced the CA1 neuron loss. We conclude that enhancement of postischemic GABA neurotransmission, during the first 2-3 days after ischemia, may reduce the ischemic CA1 damage through a continuous increase in hippocampal GABA extracellular levels (No-328), or through an increase in sensitivity to GABA neurotransmission (diazepam).
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PMID:Enhancement of GABA neurotransmission after cerebral ischemia in the rat reduces loss of hippocampal CA1 pyramidal cells. 165 87

Neuronal degeneration that occurs in both ischemia and degenerative neurologic illnesses may involve excitotoxic mechanisms. In the present study, we examined whether cortical lesions with agonists acting at subtypes of glutamate receptors result in selective patterns of neuronal death. Injections of quinolinic acid, NMDA, homocysteic acid, kainic acid (KA), and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) were made at 2 sites in the dorsolateral frontoparietal cortex in rats. After 1 week, the cerebral cortex was either dissected for neurochemical studies, or animals were perfused for histologic evaluation. Concentrations of somatostatin (SS), neuropeptide Y (NPY), substance P (SP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay, while amino acids and catecholamines were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. NMDA agonists (quinolinic acid, homocysteic acid, and NMDA itself) resulted in dose-dependent reductions in glutamate and GABA, while SS, NPY, SP, CCK, and VIP were either unchanged or significantly increased in concentration. KA and AMPA at doses that resulted in comparable GABA depletions caused significant reductions in SS concentrations. Markers of cortical afferents were spared. All excitotoxins resulted in dose-dependent marked increases in uric acid concentrations. Histologic examination verified that lesions with NMDA agonists produced relative sparing of NADPH-diaphorase, SS, VIP, and CCK neurons. These results show that NMDA excitotoxin lesions result in a pattern of selective neuronal damage in the cerebral cortex that is similar to that which occurs in both ischemia and Huntington's disease.
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PMID:Neurochemical characterization of excitotoxin lesions in the cerebral cortex. 167 Jul 82

Excitatory (glutamate, aspartate) or inhibitory amino acids (gamma-aminobutyric acid: GABA, taurine) and glutamine contents were examined in acutely induced cerebral ischemia in spontaneously hypertensive rats. At 20 min ischemia most of these amino acids remained unchanged, but glutamine significantly decreased by 14% in the CA3 hippocampal subfield. At 60 min ischemia glutamate significantly decreased by 14% in the CA3, aspartate by 17-26% in the CA3, cingulate cortex, septum and striatum. In contrast, GABA significantly increased by 48-106% in the cortices (frontal, parietal and cingulate), striatum and nucleus accumbens, but insignificantly in hippocampal subfields. Likewise, taurine increased in the parietal cortex and nucleus accumbens. Glutamine showed heterogeneous changes (increase in the nucleus accumbens and decrease in the CA3). Amino acid levels change during ischemia, but their changes are varied in each area, implying that different reaction of amino acids may explain the selective vulnerability to cerebral ischemia.
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PMID:Excitatory and inhibitory amino acid changes in ischemic brain regions in spontaneously hypertensive rats. 167 76

Ischemia of hippocampal slices leads to 86Rb+ efflux and to amino acid neurotransmitter release. This 86Rb+ efflux which corresponds to the massive K+ efflux from neuronal cells observed in ischemic animals is inhibited by glucose (IC50 = 1.7 mM). Glucose also inhibits the ischemia induced liberation of GABA and aspartate. 86Rb+ efflux is insensitive to any type of known blockers for ATP-sensitive, Ca2(+)-sensitive and voltage-sensitive K+ channels.
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PMID:K+ efflux pathways and neurotransmitter release associated to hippocampal ischemia: effects of glucose and of K+ channel blockers. 170 38

Barbiturates reduce cerebral activity which again reduce the cerebral metabolic rate probably by activating chloride channels and potentiating GABA's effects on these channels. Protection of the brain against hypoxia might theoretically occur by this mechanism, by vasoconstriction or by inhibiting calcium or glutamate. The barbiturates appear to have a positive effect in head-injury patients with high ICP uncontrollable by conventional therapy (in one study 5% of patients with a GCS < or = 7), and in animal studies of regional ischemia. No effect has been established in complete cerebral ischemia (cardiac arrest). The barbiturates have a depressant effect on the cardiovascular and respiratory systems, and the patients require intensive care. Thus there are some indications in the literature that the barbiturate treatment itself causes complications, and it is possible that this might cancel a potential beneficial effect in some patients. Clinically, the barbiturates are effective anticonvulsants, can be used in an attempt to control an elevated ICP uncontrollable by conventional means, and during transient ischemic episodes in the operating room with adequate monitoring and support systems already in place.
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PMID:Barbiturates in neuroanesthesia and neuro-intensive care. 184 34

The mongolian gerbil was introduced as a stroke model because of its incomplete circle of Willis. Unilateral carotid ligation ischemia produced in such a fashion was not effective in all gerbils. We have selected gerbils by examination of the ocular fundus to study the level of amino acids and hydroxyl free radicals (OH0 formation of DHBA, dihydroxybenzoic acid, from salicylate) in gerbil cerebral ischemia. Only gerbils with absence of retinal blood after ligation were selected as sensitive. One group (sham operated) served as control. The other group was subjected to unilateral left carotid occlusion with a clip during 30 minutes and classified as sensitive and non sensitive. Sixty minutes after release of the clip, levels of aspartate, glutamate, GABA were quantified in left hippocampus and in left retina. Levels of 2,5 DHBA (2,5 dihydroxybenzoic acid) were quantified in left retina and in left hemisphere. Compared to sham operated group, levels of aspartate (greater than 371%), glutamate (greater than 318%), GABA (greater than 122%) and 2,5 DHBA (greater than 385%) significantly increased in the group subjected to carotid occlusion. The determination of concentrations of amino acids and 2,5 DHBA in sensitive gerbils was a suitable method to study cerebral and retinal ischemia.
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PMID:Accumulation of amino acids and hydroxyl free radicals in brain and retina of gerbil after transient ischemia. 191 70

Plasma membrane potential generated by Na+, K(+)-ATPase provides the driving force for high-affinity, Na(+)-dependent uptake of glutamate into the cytoplasm of glutamatergic nerve endings and glial cells. Ca2(+)-calmodulin-dependent ATPase in the plasma membrane and Ca2(+)-ATPase in the endoplasmic reticulum influence the intracellular [Ca2+] and, therefore, the exocytotic release of neurotransmitter glutamate. The membrane potential across the membrane of the synaptic vesicles, generated by a H(+)-ATPase, provides the driving force for synaptic vesicular uptake of glutamate as well as that of GABA and glycine. Hypoxia and ischemia lead to release of glutamate, perhaps in consequence of an increased endogenous pool of glutamate and/or lack of substrate (ATP) for the ATPases. This release, rather than being exocytotic, is believed to result mainly from a reversal of the Na(+)-dependent high-affinity glutamate transporter in the plasma membrane.
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PMID:Interrelationship between glutamate and membrane-bound ATPases in nerve cells. 198 May 85

8319, ((+-)-2-Amino-N-ethyl-alpha-(3-methyl-2-thienyl)benzeneethanamine 2HCl), is a novel compound with the profile of a non-competitive NMDA antagonist. The compound displaced [3H] TCP with high affinity (IC50 = 43 nM), but was inactive at the NMDA, benzodiazepine and GABA sites; in vivo, 8319 showed good efficacy as an anticonvulsant and potential neuroprotective agent. It blocked seizures induced by NMDLA, supramaximal electroshock, pentylenetetrazol (PTZ), picrotoxin, and thiosemicarbazide with ED50's of 1-20 mg/kg ip. As a neuroprotective agent, 8319 (30-100 mg/kg sc) prevented the death of dorsal hippocampal pyramidal cells induced by direct injection of 20 nmol NMDA. At 15 mg/kg ip, the compound was also effective against hippocampal neuronal necrosis induced via bilateral occlusion of the carotid arteries in gerbils. In summary, 8319 is a noncompetitive NMDA antagonist with good anticonvulsant activity and may possess neuroprotective properties useful in the treatment of brain ischemia.
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PMID:Preclinical anticonvulsant and neuroprotective profile of 8319, a non-competitive NMDA antagonist. 229 Aug 51


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