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Extracellular levels of quinolinic acid are moderately increased in rat neostriatum following severe insulin-induced hypoglycaemia

Extracellular concentrations of the brain metabolite quinolinic acid, an endogenous excitotoxin, were monitored by microdialysis in rat neostriatum and hippocampus/cortex during and following a 30-min period of insulin-induced hypoglycaemia. During hypoglycaemia-induced isoelectricity, extracellular levels of quinolinic acid in the striatum (basal value, 1.1 ± 0.3 pmol per 30-μl fraction) were ele

Oxidative stress, mitochondrial permeability transition and activation of caspases in calcium ionophore A23187-induced death of cultured striatal neurons

Disruption of intracellular calcium homeostasis is thought to play a role in neurodegenerative disorders such as Huntington's disease (HD). To study different aspects of putative pathogenic mechanisms in HD, we aimed to establish an in vitro model of calcium-induced toxicity in striatal neurons. The calcium ionophore A23187 induced a concentration- and time-dependent cell death in cultures of embr

Blockade of the mitochondrial permeability transition pore diminishes infarct size in the rat after transient middle cerebral artery occlusion

The mitochondrial permeability transition pore is an inducer of cell death. During the reperfusion phase after cerebral ischemia, calcium accumulates in mitochondria, and a burst of free radical formation occurs, conditions that favor the activation of the mitochondrial permeability transition pore. Here the authors demonstrate that a blocker of the mitochondrial permeability transition pore, the

Changes in protein tyrosine phosphorylation in the rat brain after cerebral ischemia in a model of ischemic tolerance

A brief period of sublethal cerebral ischemia, followed by several days of recovery, renders the brain resistant to a subsequent lethal ischemic insult, a phenomenon termed ischemic preconditioning or tolerance. Ischemic tolerance was established in the rat two-vessel occlusion model of ischemia, induced by occlusion of both carotid arteries in combination with hypotension. Ischemic preconditionin

Activation of the extracellular signal-regulated protein kinase cascade in the hippocampal CA1 region in a rat model of global cerebral ischemic preconditioning

A short period of sublethal preconditioning ischemia (3 min) followed by two days of reperfusion provides almost complete protection against ischemic cell death induced by a second (9 min) lethal ischemic episode. Here, we have investigated the extracellular signal-regulated protein kinase kinase and extracellular signal-regulated protein kinase, two kinases known to activate gene transcription an

Differences in the activation of the mitochondrial permeability transition among brain regions in the rat correlate with selective vulnerability

Mitochondria from different regions of the brain were prepared, and the activation of the mitochondrial permeability transition (MPT) by calcium was investigated by monitoring the associated mitochondrial swelling. In general, the properties of the MPT in brain mitochondria were found to be qualitatively similar to those observed in liver and heart mitochondria. Thus, swelling was inhibited by ade

Activation of p53 and its target genes p21(WAF1/Cip1) and PAG608/Wig-1 in ischemic preconditioning

A brief, 3 min period of global forebrain ischemia in the rat, induced by bilateral common carotid occlusion combined with hypotension, confers resistance to hippocampal pyramidal neurons against a subsequent 10 min ischemia, which is normally lethal to these cells. The molecular mechanisms underlying this ischemic preconditioning, or tolerance, are poorly understood. The tumor suppressor p53 is a

Acidosis enhances translocation of protein kinase C but not Ca2+/calmodulin-dependent protein kinase II to cell membranes during complete cerebral ischemia

Systemic hyperglycemia and hypercapnia severely aggravate ischemic brain damage when instituted prior to cerebral ischemia. An aberrant cell signaling following ischemia has been proposed to be involved in ischemic cell death, affecting protein kinase C (PKC) and the calcium calmodulin kinase II (CaMKII). Using a cardiac arrest model of global brain ischemia of 10 min duration, we investigated the

The time-course of DNA fragmentation in the choroid plexus and the CA1 region following transient global ischemia in the rat brain. The effect of intra-ischemic hypothermia

The time-course of DNA fragmentation in the CA1 region of the hippocampus and the choroid plexus was studied following induction of transient forebrain ischemia under lethal normothermic (37°C), or sublethal hypothermic (33°C) conditions. Oligonucleosomal- and high-molecular-weight DNA fragmentation were analysed by conventional agarose gel electrophoresis and pulsed-field gel electrophoresis, res

A simple in vitro model of ischemia based on hippocampal slice cultures and propidium iodide fluorescence

This protocol describes a model of cerebral ischemia based on organotypic hippocampal slice cultures and quantitative assessment of cell death by use of propidium iodide and image analysis. The cultures were made from rat hippocampal slices that were obtained at postnatal day 4-7 and allowed to develop for > 14 days in vitro. For induction of 'in vitro ischemia', the cultures were washed in glucos

Mitochondrial permeability transition induced DNA-fragmentation in the rat hippocampus following hypoglycemia

In the present study the time-course of DNA fragmentation following insulin-induced hypoglycemia was examined. In situ localization of DNA breaks were studied by the terminal deoxynucleotidyl transferase-mediated biotin- deoxyuridine triphosphate nick-end labelling method, and the temporal profile of DNA-fragmentation by agarose gel electrophoresis. Cell nuclei displayed terminal deoxynucleotidyl

Influence of MK-801 on brain extracellular calcium and potassium activities in severe hypoglycemia

The purpose of the present study was to examine the effect of blockade of N-methyl-D-aspartate (NMDA) receptors on the depolarization associated with severe hypoglycemia, which is commonly preceded by one or a few transient depolarizations reminiscent of cortical spreading depression (CSD). In the cerebral cortices of rats [K+](e) and [Ca2+](e) were measured with ion-selective microelectrodes. NMD

Cerebral platelet thromboembolism and thromboxane synthetase inhibition

Platelet aggregating sodium arachidonate was slowly infused into the internal carotid artery (1 mg, 100 µl, 1µl/s) of nitrous oxide anesthetized rats. The electroencephalographic activity recorded by a Cerebral Function Monitor from the injected hemisphere was reduced within minutes. The so matose nsory evoked responses to contralateral electrical stimulation of the whisker area were eliminated on

Ischemic brain damage in rats following cardiac arrest using a long-term recovery model

A model is described in which transient complete cerebral ischemia is induced in rats by intracardiac injection of potassium chloride. The animals were intubated and mechanically ventilated with a nitrous oxide/oxygen (70:30) mixture. Cardiac arrest was achieved following a brief period of ventricular fibrillation. After 5-6 min, the circulation was restored by cardiopulmonary resuscitation and pa

Ischemic brain injury : The importance of calcium, lipolytic activities, and free fatty acids

Ischemic brain insults are accompanied by several metabolic alterations. In the present review, the adverse reactions, which might be important for the outcome of these insults, are those related to phospholipid and polyunsaturated fatty acid metabolism triggered by the disturbed calcium ion homeostasis in combination with energy depletion following ischemia. These conditions lead to an activation