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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protective effect and mechanism of diazepam on ischemia neurons during cerebral ischemia and reperfusion were studied. Sixty-three Wistar rats were divided randomly into nine groups: control group (n = 7), ischemia (is) groups including subgroups of is3 h, is3-h/rep1-h, is3-h/rep2-h, is3-h/rep3-h(n = 7 in each group), diazepam treated groups (10 mg/kg, i.p.), including subgroups of is3-h, is3-h/rep1-h, is3-h/rep2-h, is3-h/rep3-h (n = 7 in each group) with Zea longa's animal model of middle cerebral artery occlusion. The comparison between the ischemia group and diazepam-treated group showed that diazepam could obviously decrease the production of glutamate, asparate, MDA and increase the synthesis and release of GABA, SOD and GSH-PX. It was concluded that diazepam exerted its protective effects on neurons through complex mechanisms of regulating the synthesis and release of excitotary/inhibitory amino acids and free radicals.
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PMID:Effect of diazepam on the contents of amino acids and free radical during ischemia/reperfusion injury. 1152 8

Intracerebral MD enables the retrieval of endogenous substances from the extracellular fluid (ECF) of the brain and has been demonstrated to be a sensitive technique for early detection of subtle vasospasm-induced neurometabolic abnormalities in patients with subarachnoid hemorrhage (SAH). The aim of this study was to monitor cortical extracellular concentrations of energy metabolism markers, such as glucose and lactate, neurotransmitter amino acids, such as glutamate, aspartate, GABA and taurine to identify any neurochemical patterns of cerebral ischemia. A prospective clinical study was conducted on a group of 16 patients with non-severe SAH operated on within 72 hours after initial bleeding. Following aneurysm clipping, an MD catheter was inserted in the cortical region where vasospasm could be expected to develop, and perfused with artificial CSF at 0.3 microl/min flow rate. Dialysate was collected every 6 hours and then analyzed on High Performance Liquid Cromatography (HPLC) for glucose, lactate, pyruvate, glutamate, aspartate, GABA and taurine. Mean ECF taurine concentrations ranged from 1.4 + 0.7 to 12.3 + 7.8 micromol/l in single patients: global mean value was 5.8 + 3.8 micromol/l. In this series, the highest absolute taurine value was 25.7 micromol/l, observed in a patient who developed clinical and radiological signs of cerebral ischemia. Nine patients presented clinical disturbances related to cerebral vasospasm. In this setting, representing a mild-to-moderate hypoxic condition, MD data demonstrated that lactate is the most sensitive marker of cellular energy imbalance. Increased lactate levels positively correlated with glutamate (P<0.0001), aspartate (P<0.0001), GABA (P<0.0001) and taurine (P<0.0001) concentrations. These results suggest that also in humans increased taurine levels reflect a condition of cellular stress. This study confirms that MD is a sensitive technique to reveal subtle metabolic abnormalities possibly resulting in cell damage.
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PMID:Post-operative monitoring of cortical taurine in patients with subarachnoid hemorrhage: a microdialysis study. 1178 46

Loss of inhibitory GABAergic modulation may induce hyperexcitability of neuronal elements and potentiate their vulnerability to excitotoxic injury. It has been also found that the adenosine system interacts with the GABAergic system during ischemia and anoxia where the adenosine receptors as well as the GABAergic receptors may conscript the same intracellular pathway to increase tolerance to ischemia. Therefore, it was aimed to study whether dipyridamole (CAS 58-32-2), an adenosine uptake inhibitor, or adenosine (CAS 58-61-7) could affect the rat brain gamma-aminobutyric acid (GABA, CAS 56-12-2) level after induction of cerebral ischemia, and to test their effect on the lactate dehydrogenase (LDH) activity of the ischemic rat brain. Ischemia was induced by bilateral clamping of the common carotid arteries for 60 min followed by reperfusion for other 60 min. Dipyridamole was administered alone and in combination with adenosine and the effect of the drugs on the brain GABA level as well as on LDH activity was determined. The results show that dipyridamole could protect the brain of rats against the ischemic insult, while adenosine when administered separately failed to influence the selected parameters. Protection of the rat brain by dipyridamole might be related to the elevated level of GABA.
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PMID:Influence of inhibition of adenosine uptake on the gamma-aminobutyric acid level of the ischemic rat brain. 1208 19

Selective antagonists of mGlu1 metabotropic glutamate receptors attenuate neuronal death in models of cerebral ischemia. Because GABAergic mechanisms have recently been proposed to contribute to these neuroprotective effects, we examined the effects of selective mGlu1 antagonists characterized in our laboratory on GABAergic transmission in three different models of neuropathology. In rat organotypic hippocampal slices exposed to oxygen-glucose deprivation, the mGlu1 antagonists AIDA, CBPG and 3-MATIDA reduced CA1 pyramidal cell loss when added to the medium during the insult and the subsequent recovery period. This effect was mimicked by the GABA(A) and GABA(B) agonists muscimol and baclofen and partially prevented by the antagonists bicuculline and CGP 55845. In gerbils subjected to global ischemia, protection of CA1 pyramidal cells by transdialytic perfusion of AIDA and CBPG was associated with a significant increase in the basal and ischemic output of GABA and minor changes in the output of glutamate. In a mouse cortical wedge model, both muscimol and 3-MATIDA reduced the frequency of spontaneous bursts induced by 4-aminopyridine and this reduction was prevented by co-perfusion with bicuculline. Taken together, our results suggest that the release of GABA, and the subsequent activation of GABA receptors, may contribute to the attenuation of post-ischemic neuronal damage and epileptiform activity induced by mGlu1 receptor antagonists.
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PMID:Metabotropic glutamate 1 (mGlu1) receptor antagonists enhance GABAergic neurotransmission: a mechanism for the attenuation of post-ischemic injury and epileptiform activity? 1221 66

We hypothesized that static skeletal muscle contraction-induced systemic cardiovascular responses, and central glutamate/GABA release in rostral (RVLM) and caudal ventrolateral medulla (CVLM), would be modulated by cerebral ischemia. In sham-operated rats, a 2-min tibial nerve stimulation induced static contraction of the triceps surae, evoked pressor responses, increased glutamate in both the RVLM and CVLM, decreased GABA in the CVLM, and increased GABA in the RVLM. In rats with a temporary 90-min left middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion, pressor responses during muscle contractions were attenuated, as were glutamate within the left RVLM and left CVLM. Glutamate within the right RVLM and right CVLM were unaltered and similar to those in sham rats. In contrast, GABA increases during muscle contractions were enhanced in the left RVLM and CVLM but changes within the right CVLM and RVLM were similar to those in sham rats. These results indicate that unilateral ischemia increases ipsilateral GABA/glutamate ratios during muscle contraction in the RVLM. In contrast, opposite changes in ipsilateral glutamate and GABA release within the RVLM and CVLM were observed following a 90-min right-sided MCAO followed by 24 h reperfusion. However, cardiovascular responses during muscle contraction were depressed following such an ischemic brain injury. These data suggest that transient ischemic brain injury attenuates cardiovascular responses to static exercise via modulating neurotransmission within the ventrolateral medulla.
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PMID:Cardiovascular responses and neurotransmission in the ventrolateral medulla during skeletal muscle contraction following transient middle cerebral artery occlusion and reperfusion. 1237 78

Neuronal cells are susceptible to cerebral ischaemia. As gamma-aminobutyric acid(A) (GABA(A)) receptors are specific for neurones, functional receptor imaging using I-iomazenil (IMZ), a ligand to the GABA benzodiazepine receptor, has been proposed as an imaging modality for the assessment of neuronal integrity. However, there is only limited experience with IMZ in patients with acute cerebral infarction. Therefore, the aim of this study was to evaluate IMZ single photon emission computed tomography (SPECT) in patients with acute cerebral ischaemia. IMZ SPECT was performed in 21 patients with acute cerebral infarction 7-10 days after stroke onset. Eleven patients underwent systemic thrombolysis within 6 h after symptom onset (group 1), whereas 10 patients were treated conservatively (group 2). IMZ (150-200 MBq) was injected intravenously and imaging was performed using a dedicated four-head SPECT camera at 5 min (perfusion) and 90 min (receptor distribution) post-injection, with an acquisition time of 50 min each. Images were analysed by visual inspection. Four patients showed normal IMZ distribution, and 17 patients showed abnormalities of IMZ uptake on both early and late images. In six patients with regional uptake deficits, a crossed cerebellar diaschisis was observed on early images. Cerebellar inhomogeneity of tracer uptake was absent at the time of late images in all six patients. In eight patients, areas of hypoperfusion corresponded exactly to the regions of receptor deficiency (match). In five patients, preserved neuronal integrity was present in hypoperfused areas (mismatch). In four patients, normally or even hyperperfused areas exhibited regional receptor deficiency (inverse mismatch). In conclusion, IMZ SPECT demonstrated differences between regional perfusion and receptor distribution in about one-half of patients 7-10 days after acute cerebral ischaemia. Interesting patterns between the early phase (perfusion) and the late phase (receptor distribution) were found. These patterns are indicative of the heterogeneous development of cerebral ischaemia where, even days after stroke onset, areas of hypoperfusion but preserved neuronal integrity may be present. However, the evaluation of the potential clinical and therapeutic impact of individual IMZ distribution patterns requires further investigation.
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PMID:Experience with 123I-iomazenil SPECT in acute cerebral infarction. 1246 84

We have previously shown that exogenous application of brain-derived neurotrophic factor (BDNF) reduces infarct volume in the cortical ischemic penumbra after experimental focal ischemia [Stroke 31 (2000) 2212-2217]. Since BDNF is known to modulate the expression and function of various neurotransmitter receptors, we addressed the question whether BDNF may act via modification of postischemic ligand binding to excitatory NMDA and AMPA and/or inhibitory GABA(A) receptors, respectively. Transient focal cerebral ischemia was induced in male Wistar rats for 2 h using the suture occlusion technique. A period of 30 min after occlusion of the middle cerebral artery, BDNF (300 microg/kg per hour in vehicle; n=5) or vehicle alone (n=5) was continuously infused intravenously for 3 h. Using quantitative receptor autoradiography, postischemic ligand binding of [(3)H]MK-801, [(3)H]AMPA and [(3)H]muscimol was analyzed in the ischemic core, the ischemic cortical penumbra and corresponding regions of the contralateral hemisphere. Transient focal ischemia caused a significant reduction of [(3)H]muscimol binding to GABA(A) receptors within the ischemic cortical penumbra of placebo-treated rats. This was largely prevented by exogenous application of BDNF. [(3)H]MK-801 and [(3)H]AMPA binding values were also reduced in the cortical penumbra and the corresponding area of the contralateral hemisphere. Our data suggest that the neuroprotective effect of BDNF against ischemic damage in the cortical penumbra may be mediated in part by maintained activity of the inhibitory GABAergic system which likely counteracts glutamate induced excitotoxicity.
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PMID:Exogenous brain-derived neurotrophic factor prevents postischemic downregulation of [3H]muscimol binding to GABA(A) receptors in the cortical penumbra. 1265 2

An efficient, sensitive and rapid analysis of the amino acid neurotransmitters in the cerebral cortex of rats was developed by capillary electrophoresis with laser-induced fluorescence detection and fluorescein isothiocyanate (FITC) derivatization. This method was used to investigate the pharmacological effect of baicalin during cerebral ischemia. Different parameters which influenced derivatization and separation were optimized. The separation of amino acids was carried out in an uncoated fused-silica capillary (57 cm x 75 microm I.D.) with a buffer of 15 mM borate at pH 9.2 and an applied voltage of 17.5 kV. The detection limits for six amino acids were in the range of 2.1 x 10(-11)-6.3 x 10(-10) M. The changes in the level of amino acid neurotransmitters in brain cortex of three experimental rat groups were studied by this capillary electrophoresis-laser-induced fluorescence detection method. The results show that cerebral ischemia can cause a significant elevation in the concentrations of Glu, Asp, GABA, and Gly in cerebral cortex. Baicalin administration can attenuate the elevations of Glu and Asp induced by cerebral ischemia. This research demonstrates that baicalin may act as a neuroprotectant during cerebral ischemia.
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PMID:Determination of amino acid neurotransmitters in cerebral cortex of rats administered with baicalin prior to cerebral ischemia by capillary electrophoresis-laser-induced fluorescence detection. 1266 75

Elucidation of the metabolism and pharmacology of 1,2,3-triazolines (TRs) led to the identification of the triazoline pharmacophore and the evolution of the aminoalkylpyridines (AAPs). The AAPs have no activity in the scMet test but are highly effective in the MES seizure test by the oral route. The AAPs bind to the sigma(1) receptor with low affinity, but high selectivity. They impair Glu release to the same extent as the triazolines and afforded a high degree of protection in the kindled rat. They show no affinity for the NMDA/PCP receptor sites; thus the toxic side effects of NMDA antagonists are absent in the sigma selective AAPs. Variations of the heterocyclic unit, the alkyl chain and the amino group in the AAP leads, indicated that the 4-pyridyl substituent along with a methyl (alkyl) group, and a 4-C1, 3-C1 or 3,4-C1(2) substitution on the N-phenyl group, afforded the most active compounds. Amino group modification by acylation did not improve activity. The hydrazone compounds were the most active. Although the AAPs are very effective in the MES and the kindling models of epilepsy, they showed only low to moderate activity in protecting neuronal cells in stroke-induced cerebral ischemia. In the case of the TR compounds, even the least effective TR afforded 47% protection from neuronal injury. It is not known at this point, whether activity in both the MES and scMet tests, which would imply a role for both Glu and GABA, is a prerequisite for antiischemic activity.
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PMID:Aminoalkylpyridines (AAPs), triazoline metabolite analogues, as anticonvulsants highly effective in the MES test. 1287 Oct 88

Sudden cessation of blood flow to the brain results in a series of events that either result in rapid loss of brain cells or delayed neuronal injury in certain vulnerable regions of the brain. Research over the last three decades has allowed for a better understanding of how neurons and other brain cells die from the effects of ischemia and hypoxia in the central nervous system. Excitatory and inhibitory neurotransmitters exist in a very precise balance for normal function of the brain. Ischemia very rapidly disrupts this balance resulting in a rapid build-up of excitatory neurotransmitters, especially glutamate in the extracellular space. The increased glutamate together with energy loss opens a number of different types of calcium and sodium channels resulting in the build-up of these ions in neurons, leading to cellular dysfunction and death. While most ischemia research has focused on antagonism of excitatory amino acids, there are some reports on enhancement and amplification of inhibitory responses in focal and global ischemia. The majority of work relates to potentiation of GABA, either endogenous or through GABA potentiating medications. Taurine has neuroinhibitory properties and may also have potential for neuroprotection in cerebral ischemia. This present review focuses on the role of taurine as a neuroprotective agent, possibly acting through several different inhibitory mechanisms. Taurine may inhibit neurotransmitter release and may result in normal intracellular osmolality. In transient global ischemia in gerbils, we studied in vivo microdialysis of amino acids before, during and after ischemia. We were able to show that taurine resulted in attenuation of glutamate during ischemia (however did not reach significance). In similar experiments, neuronal damage was assessed in the hippocampus. Our results show 48% damage in taurine treated animals, 60% in alanine treated animals and 69% in control groups (trend towards protection but again did not reach significance) Focal ischemia was induced by embolizing a thrombus into the distal internal carotid artery and origin of the middle cerebral artery. Again, in studies where we compared taurine to a placebo treated animal, there was no significant decrease in the amount of damage with taurine. There are reports in the literature that taurine may attenuate neuronal injury during ischemia. Our studies in two models of cerebral ischemia in rodents did not reveal neuronal protection. It is possible that higher doses or possibly prolonged use of taurine may show better results. Taurine may also potentially offer additive protective effects when used in combination with thrombolysis or other neuroprotective agents. Further studies are necessary to better understand the potential for taurine as a neuroprotective agent in cerebral ischemia.
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PMID:The role of taurine in cerebral ischemia: studies in transient forebrain ischemia and embolic focal ischemia in rodents. 1290 27


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