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

The effects of arachidonic acid and its metabolites on gamma-aminobutyric acid (GABAA) receptor function were determined in rat cerebral cortical synaptoneurosomes. Incubation of synaptoneurosomes with phospholipase A2 decreased muscimol-induced 36Cl- uptake. Arachidonic acid, the major unsaturated fatty acid released by phospholipase A2, also inhibited muscimol-induced 36Cl uptake. Similar inhibition was obtained with other unsaturated fatty acids (docosahexaenoic, oleic) but not with saturated fatty acids (stearic, palmitic). The effect of arachidonic acid on muscimol responses was inhibited by bovine serum albumin (BSA), and BSA enhanced muscimol responses directly, indicating the generation of endogenous arachidonic acid in the synaptoneurosome preparation. The generation of endogenous arachidonic acid was also indicated by the ability of 2 inhibitors of arachidonic acid metabolism, indomethacin and nordihydroguaiaretic acid (NDGA), to inhibit muscimol-induced 36Cl uptake. We conclude that arachidonic acid probably has both direct and indirect actions on muscimol responses since both enzyme inhibitors inhibited muscimol responses but did not prevent the effect of exogenously added arachidonic acid. In additional experiments, arachidonic acid metabolites generated by cyclooxygenase, prostaglandins D2, E2 and F2 alpha, each decreased muscimol responses; prostaglandins F2 alpha was the most potent inhibitor. Since the unsaturated fatty acids and their metabolites are most susceptible to peroxidation, a generating system of superoxide radicals was tested on muscimol responses. A combination of xanthine and xanthine oxidase inhibited muscimol-induced 36Cl uptake in a concentration-dependent manner. We propose that the inhibition of GABAA neurotransmission by arachidonic acid and its metabolites can lead to increased neuronal excitability. This mechanism may play an important role in the development of neuronal damage following seizures or cerebral ischemia.
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PMID:Inhibition of GABA-gated chloride channel function by arachidonic acid. 132 73

We investigated the extravasation of serum albumin using immunohistochemistry in three different conditions, i.e., infarction, selective neuronal death and selective loss of presynaptic terminals following cerebral ischemia in gerbils. In selective neuronal death, which is typically found in the CA1 neurons of the hippocampus after 5-min bilateral cerebral ischemia, selective damage of postsynaptic components with intact presynaptic sites was demonstrated by immunohistochemical examination for microtubule-associated protein 2 and synapsin I, and albumin extravasation did not become apparent before postsynaptic structures were destroyed. In cerebral infarction, which was consistently observed in the thalamus after 15-min forebrain ischemia, massive albumin extravasation was visible early after ischemia due probably to the ischemic endothelial necrosis. In selective loss of presynaptic terminals, which was detected at the molecular layer of the dentate gyrus in the contralateral, nonischemic hippocampus after unilateral cerebral ischemia, immunoreaction for albumin was not visualized. Since endothelium and glial cells were intact in morphological aspects in selective damage of both pre- and postsynaptic sites, it was thought that extravasation was facilitated by the stimulation of endothelial cells and glial cells with unknown factors that were induced by the destruction of post- but not presynaptic elements.
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PMID:The characteristics of blood-brain barrier in three different conditions--infarction, selective neuronal death and selective loss of presynaptic terminals--following cerebral ischemia. 144 19

The blood-brain barrier breaks down following cerebral ischemia, but the exact sequence of events for extravasation of serum proteins and their parenchymal distribution remain uncertain. We studied the distribution of serum albumin in the hippocampus of the gerbil brain using light and electron microscopic immunocytochemical techniques. With light microscopy, there was no reaction for albumin for the first 12 h after unilateral common carotid artery occlusion for 10 min and reperfusion. At 12 h, the reaction was weak and limited to the neuropil in the subiculum-CA1 region (between the subiculum and the medial CA1 region). After 24 h, the reaction became intense in the neuropil and neuronal perikarya in the subiculum-CA1 and medial CA1 regions. The electron microscopic immunocytochemical study of the subiculum-CA1 and medial CA1 regions revealed electron-dense immunoprecipitates in the extracellular space and the peripheral part of the apical dendrites as early as 30 min after reperfusion and in the astrocytic cytoplasm after reperfusion for 1 h. However, immunoprecipitates were not found in the neuronal perikarya until after reperfusion for 24 h. The present study demonstrated prompt appearance of albumin in the extracellular space of the brain parenchyma after re-establishment of cerebral circulation and prompt accumulation in the peripheral part of the dendrites with spreading to neuronal perikarya, likely in the process of degeneration and death.
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PMID:Intracerebral distribution of albumin after transient cerebral ischemia: light and electron microscopic immunocytochemical investigation. 150 82

Focal cerebral ischemia was produced by occluding the left middle cerebral artery in 769 rats. Permeability of the blood-brain barrier to small or large molecules was evaluated qualitatively using Evans blue or sodium fluorescein and quantitatively using the transfer indexes of iodine-125-labeled bovine serum albumin or [14C]sucrose. Water content was determined using wet and dry weights and sodium and potassium contents using flame photometry. Cortical tissue in the middle cerebral artery territory was sampled less than or equal to 14 days after occlusion. A significant increase in the albumin transfer index was first found 12 hours after occlusion, and the index remained approximately the same until water content peaked 3 days after occlusion. In contrast, the sucrose transfer index increased gradually, significantly correlated with increases in the water and sodium contents. Tissue staining by sodium fluorescein was more extensive than that by Evans blue. As edema fluid decreased gradually 4-10 days after occlusion, the albumin and sucrose transfer indexes increased markedly. These findings indicate that disruption of the blood-brain barrier to small molecules is accompanied by accumulation of edema fluid during the later stages of ischemia. Opening of the barrier to serum protein is probably related to the resolution of edema.
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PMID:Brain edema and cerebrovascular permeability during cerebral ischemia in rats. 169 34

Hypovolemic patients are more likely to suffer delayed cerebral ischemia and infarction after a subarachnoid hemorrhage (SAH). Prompt recognition and correction of hypovolemia may improve the outcome. We have identified computed tomographic (CT) scan findings that increase the probability of a patient presenting with hypovolemia soon after an SAH. The plasma volume (PV) of 25 patients admitted within 96 hours of an SAH was measured using radioiodinated serum albumin. The normal PVs were measured in an outpatient setting 6 months later or predicted from their total body water. Nine patients (36%) were found to be hypovolemic, defined as a fall in PV exceeding 10% of the normal PV (mean fall, 18 +/- 2%). Sixteen patients were normovolemic or hypervolemic (mean PV, +9 +/- 2%). The basal cisterns were compressed or obliterated on the CT scans of all hypovolemic patients compared with 12.5% of normovolemic patients (chi-square, 14.52; P less than 0.01). The probabilities of a patient being hypovolemic if the CT scan indicated raised intracranial pressure were high: hydrocephalus, P = 0.80; compression of the basal cisterns, P = 0.82; and compression of the basal cisterns associated with intracerebral hematoma or midline shift, P = 1.00. Patients with an SAH and radiological evidence of raised intracranial pressure should be considered at particular risk for systemic hypovolemia.
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PMID:Association of hypovolemia after subarachnoid hemorrhage with computed tomographic scan evidence of raised intracranial pressure. 188 54

We investigated the temporal profile of the extravasation of serum albumin in a reproducible gerbil model of unilateral cerebral ischemia, using immunohistochemical and dye-tracer techniques to evaluate albumin accumulation and the occurrence of active extravasation, respectively. After 30 min of cerebral ischemia and subsequent reperfusion, immunostaining for albumin became visible in the lateral part of the thalamus during the first 3 h, and then expanded to other brain regions up to 24 h. At both 24 h and 3 days after reperfusion, massive extravasation of albumin was noted in the whole ischemic hemisphere, and this had decreased again by 7 days after reperfusion. The extent and the degree of albumin immunopositivity were almost the same in all animals examined at each period after reperfusion. The extravasation of Evans blue, which was allowed to circulate for 30 min before death, was limited to the lateral part of the thalamus during the first 6 h of reperfusion. In the circumscribed area of massive albumin extravasation, many neurons were immunopositive for albumin; most of these neurons appeared to be intact and also showed immunostaining for microtubule-associated protein 2. The current investigation clearly demonstrated that (1) albumin extravasation was produced with reliable reproducibility in this model, (2) the lateral part of the thalamus was the region most vulnerable to ischemic blood-brain barrier damage, and (3) many apparently intact neurons in the ischemic region were positive for albumin.
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PMID:Temporal profile of serum albumin extravasation following cerebral ischemia in a newly established reproducible gerbil model for vasogenic brain edema: a combined immunohistochemical and dye tracer analysis. 192 73

Potential involvement of neuroexcitatory mechanisms was studied in: 1) repetitive forebrain ischaemia in gerbils, 2) global cerebral ischaemia in rats and 3) cryogenic injury to the cerebral cortex in rats and gerbils. Uptake of 45Ca was used as a marker of injury, whereas ultrastructural localization of calcium was assessed with an oxalate-pyroantimonate method. The blood-brain barrier was evaluated with immunostaining for serum albumin. Changes in extracellular glutamate were estimated by microdialysis and an enzymatic cycling assay. Changes in water content were assessed by specific gravity measurements. Repetitive ischaemia of 3 x 5 min carotid occlusions produced a cumulative effect with regard to development of oedema and neuronal injury. This was associated with several-fold increments in glutamate release after repeated insults, whereas there was no apparent correlation with energy metabolism disturbances. Other studies revealed in all models a development of secondary foci distant to the primary impact of ischaemia or cold lesions, which were characterized by calcium accumulation in swollen dendrites, chronic neuronal changes and intraneuronal uptake of serum proteins, all of these changes being potentially compatible with involvement of neuroexcitatory mechanisms.
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PMID:Role of neuroexcitation in development of blood-brain barrier and oedematous changes following cerebral ischaemia and traumatic brain injury. 198 78

Progressive stenosis or occlusion of bilateral internal carotid arteries by fibrocellular intimal thickening results in cerebral ischemia in moyamoya disease. The etiology is unknown. We examined cultured arterial smooth muscle cells (SMC) from scalp arteries of five patients with moyamoya disease. In this study we investigated the responsiveness of the cells in culture to serum mitogens including platelet-derived growth factor (PDGF), a major mitogen of SMC, and compared the response to that of cells derived from age-matched control patients. SMC from patients with moyamoya disease proliferated less rapidly in a medium with 15% serum than did control SMC and responded poorly to the addition of PDGF to 5% serum. PDGF alone did not stimulate SMC in a quiescent state to initiate DNA synthesis in moyamoya disease, without serum factors other than bovine serum albumin, though it significantly stimulated the controls. Simultaneous additions of epidermal growth factor, insulin-like growth factor-I, and PDGF stimulated initiation of DNA synthesis in cells from moyamoya disease, but not as much as PDGF alone did in the controls. Although direct correlations with the pathogenesis of the disease remain to be clarified, the results indicate altered interrelations between serum factors and the cellular responses in vessels of moyamoya disease.
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PMID:Altered cellular responses to serum mitogens, including platelet-derived growth factor, in cultured smooth muscle cells derived from arteries of patients with moyamoya disease. 204 Jun 53

Polyunsaturated fatty acids (PUFAs), arachidonic acid in particular, are well known, potent inducers of edema in the brain, while monounsaturated and saturated long chain fatty acids do not possess this quality. This investigation has compared the ability of some free fatty acids (FFAs), known to be released during cerebral ischemia, to induce brain mitochondrial swelling in vitro. The PUFAs tested, especially arachidonic acid (20:4), were more potent in causing swelling than saturated or monounsaturated ones, as measured by the decrease in light absorbance of the mitochondrial suspension. This finding is in line with the unique potency of 20:4 to induce brain edema. Incubation of brain mitochondria with 20:4 for 20 min caused a dose-dependent swelling. ATP-MgCl2 both prevented and reversed this swelling, while binding of the 20:4 by the addition of bovine serum albumin could only prevent but not reverse the swelling. The contraction of the swollen mitochondria appeared to be mediated by a mechanism dependent upon high-energy phosphates, potentiated by MgCl2. The concentration of 20:4 required to induce swelling was about 20 times higher than the concentration required to induce inhibition of mitochondrial respiratory function (L Hillered and P H Chan: J Neurosci Res 19:94-100, 1988a). Moreover, reversal of the swelling occurred without recovery of respiratory function. These results suggest that swelling is a phenomenon of minor importance as an indicator of brain mitochondrial dysfunction, at least when induced by 20:4 in vitro.
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PMID:Brain mitochondrial swelling induced by arachidonic acid and other long chain free fatty acids. 253 Dec 32

The present investigation was designed to examine the effects of free arachidonic acid (20:4), in concentrations relevant to cerebral ischemia, on brain mitochondrial respiratory activities and the reversibility of these effects. Incubation of brain mitochondria with 20:4 caused a dose-dependent increase in substrate-supported (state 4) respiration (i.e., uncoupling) and a concomitant inhibition of substrate-, phosphate-, and ADP-supported (state 3) or dinitrophenol-supported state (3u) respiration. The temperature dependence of the 20:4 effects on mitochondrial respiration was also studied. It was found that the uncoupling and the respiratory inhibition were at least as pronounced at physiological temperatures as at room temperature. Arrhenius plots of the state 3 respiratory rates suggested that 20:4 did not cause a significant change in membrane fluidity. Addition of bovine serum albumin to the reaction medium following preincubation with 20:4 reversed the uncoupling effect but only partly reversed the inhibition of state 3 respiration. The results suggest 1) that 20:4 may inhibit mitochondrial ATP production during conditions of incomplete cerebral ischemia and 2) that 20:4 may limit the postischemic recovery of mitochondrial function.
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PMID:Effects of arachidonic acid on respiratory activities in isolated brain mitochondria. 312 46


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