UMLS:C0917798 - FACTA Search

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

The dramatic increase in the arachidonic acid (AA) level in the brain is a well-known molecular event during cerebral ischemia. As mitochondria are known to be one possible site of the cell damage, the effects of AA on the respiratory activity of rat brain mitochondria were investigated in vitro using an oxygen electrode. In NAD-linked respiration, respiratory control ratio was decreased significantly by AA, with an IC50 of 6.0 microM. AA had the dual effect on mitochondrial respiration, a decrease in state 3 and uncoupled state and an increase in state 4 (i.e., uncoupling) as reported by Hillered and Chan (J. Neurosci. Res. 19, 94-100, 1988). Furthermore, we found that other unsaturated long-chain free fatty acids (C18:1-C18:3, C20:1-C20:5) also showed such a dual effect. Cyclooxygenase metabolites of AA such as prostaglandins (D2, E2, F2 alpha, E1) and thromboxane B2, and lipoxygenase metabolites such as leukotrienes (D4, B4) and 5- or 12-hydroperoxyeicosatetraenoic acid had no significant effect. The inhibition of the uncoupled state by AA was more marked in NAD-linked than that in FAD-linked respiration, while the degree of uncoupling by AA were the same in both respirations. In spectrophotometrical measurement, the reduction of cytochromes and flavo-protein was markedly inhibited by AA in NAD-linked respiration, but not in the FAD-linked one. In addition, the activity of cytochrome c oxidase was scarcely inhibited by AA. These data suggest that AA itself, not its metabolites, may inhibit mitochondrial ATP production during brain ischemia and that AA may act on the site(s) closely related to NAD-linked respiration, but not the FAD-linked one, in addition to its uncoupling effect.
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PMID:A possible mechanism of mitochondrial dysfunction during cerebral ischemia: inhibition of mitochondrial respiration activity by arachidonic acid. 165 47

Bradykinin (BK) is known to be involved in the inflammatory process causing various tissue reactions such as peripheral vasodilation and increased vascular permeability. The aims of this study was to investigate the involvement of the kallikrein-kinin system (K-K system) in the generation and progression of cerebral edema following an ischemic incident. First, after infusion of BK into the internal carotid artery, the cerebral water content was measured and electron microscopic observations were made to investigate changes of permeability using the horseradish peroxidase (HRP) tracer method. Secondly, the plasma and tissue BK levels, cerebral water content and energy metabolites (ATP, lactate and pyruvate) were measured at scheduled intervals. This was achieved using the cerebral ischemia model induced in spontaneously hypertensive rats (SHR) in which the common carotid artery were occluded (BLCO) with clips in both sides. The plasma and tissue BK were measured by radioimmunoassay. Furthermore, aprotinin and soybean trypsin inhibitor (SBTI), which specifically inhibit the K-K system, were applied to the same model and the effects on cerebral edema and metabolism were tested. At three hours after infusion of BK, cerebral edema was observed on the infused hemisphere and an increase of pinocytosis in the vessels was observed in the electron microscopic study. The chronological observation of cerebral water content revealed that it started to increase after BLCO, reaching a peak level at 30 min after reperfusion, before decreasing slightly. The plasma BK levels also showed an increase at the end of BLCO and reached a peak level at 30 min after reperfusion, decreasing thereafter. The tissue BK levels elevated significantly at 30 min after reperfusion and returned to control levels at 60 min. The ATP levels decreased remarkably after BLCO, and then increased after 30 min of reperfusion. The lactate levels increased during ischemia and became higher at 30 min after reperfusion and then decreased. The pyruvate levels did not change during this time period. In the treated group, aprotinin showed significantly lower levels of cerebral water content compared to the control. This group also showed lower lactate accumulation and preservation of ATP levels than the control. SBTI also had significantly lower water content than the control, but there was no difference in the metabolites. These results showed that BK augments the progression of brain edema and that the BK level corresponded with progression of ischemic brain edema and the suppression of BK decreased edema formation. These novel findings indicate a close relationship between BK and ischemic brain edema.
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PMID:[Studies on the involvement of bradykinin in the formation of ischemic brain edema]. 169 63

Marked hyperemia accompanies reperfusion after ischemia in the brain, and may account for the propensity of cerebral hemorrhage to follow embolic stroke or carotid endarterectomy, and for the morbidity that follows head injury or the ligation of large arteriovenous malformations. To evaluate the contribution of trigeminal sensory fibers to the hyperemic response, CBF was determined in 12 symmetrical brain regions, using microspheres with up to five different isotopic labels, in four groups of cats. Measurements were made at 15-min intervals for up to 2 h of reperfusion after global cerebral ischemia induced by four-vessel occlusion combined with systemic hypotension of either 10- or 20-min duration. In normal animals, hyperemia in cortical gray matter 30 min after reperfusion was significantly greater after 20 min (n = 10) than after 10 min (n = 7) of ischemia (312 ml/100 g/min versus 245 ml/100 g/min; p less than 0.01). CBF returned to preischemic levels approximately 45 min after reperfusion and was reduced to approximately 65% of basal CBF for the remaining 75 min. In cats subjected to chronic trigeminal ganglionectomy (n = 15), postocclusive hyperemia in cortical gray matter was attenuated by up to 48% on the denervated side (249 versus 150 ml/100 g/min; p less than 0.01) after 10 min of ischemia. This effect was maximal in the middle cerebral artery (MCA) territory, and was confined to regions known to receive a trigeminal innervation. In these animals, substance P (SP) levels in the MCA were reduced by 64% (p less than 0.01), and the density of nerve fibers containing calcitonin gene-related peptide (but not vasoactive intestinal polypeptide or neuropeptide Y) was decreased markedly on the lesioned side. Topical application of capsaicin (100 nM; 50 microliters) to the middle or posterior temporal branch of the MCA 10-14 days before ischemia decreased SP levels by 36%. Postocclusive hyperemia in cortical gray matter was attenuated throughout the ipsilateral hemisphere by up to 58%, but the cerebral vascular response to hypercapnia (PaCO2 = 60 mm Hg) was unimpaired. The duration of hyperemia and the severity of the delayed hypoperfusion were not influenced by trigeminalectomy, capsaicin application, or the intravenous administration of ATP. These data demonstrate the importance of neurogenic mechanisms in the development of postischemic hyperperfusion, and suggest the potential utility of strategies aimed at blocking axon reflex-like mechanisms to reduce severe cortical hyperemia.
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PMID:Chronic trigeminal ganglionectomy or topical capsaicin application to pial vessels attenuates postocclusive cortical hyperemia but does not influence postischemic hypoperfusion. 170 54

We measured the parameter lambda, which is the ratio of the distribution spaces of 2-deoxy-D-glucose (DG) and glucose in the brain, in a model of focal cerebral ischemia in the cat. lambda is the parameter in the lumped constant of the [14C]DG technique most susceptible to changes in ischemia. Cats were subjected to occlusion of the middle cerebral artery for a period of 2 h. During the last 60 min of occlusion, [14C]DG was infused in a programmed fashion so as to obtain a stable arterial blood [14C]DG concentration. The brain was funnel-frozen to preserve tissue metabolites and the frozen brain was sampled regionally (4 to 7-mg samples) for local concentrations of glucose, ATP, phosphocreatine (PCr), and lactate. In a separate series of cats, the infusion of [14C]DG was started after 2 h of occlusion and 3 h of recirculation. In both series, lambda declined slightly for increased levels of tissue glucose and increased appreciably as tissue glucose decreased. A similar relationship was observed between lambda and ATP and PCr, although the correlation was not as clear. Since lambda, and hence the lumped constant, increases in ischemia as well as in postischemic tissue, it is important to measure tissue glucose concentration if quantitative values of local cerebral glucose metabolism are desired in this condition.
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PMID:Effect of ischemia and reperfusion on lambda of the lumped constant of the [14C]deoxyglucose technique. 172 44

We examined the effects of a new hyperosmotic agent (NIK-242inj.) on brain edema, energy metabolites and regional cerebral blood flow (r-CBF) during acute cerebral ischemia. Cerebral ischemia was induced by bilateral common carotid artery ligation (BLCL) using spontaneously hypertensive rats (SHR). The experimental animals were divided into 4 groups, A:20% NIK-242inj., B:20% mannitol, C:10% glycerol in 5% fructose, D:normal saline. All the animals were administered the agent or saline intravenously beginning at 1h after BLCL and continuing for 2h for a total dose of 6.8 ml/kg body weight. Brain water content and metabolites (ATP, lactate, pyruvate) were determined 3h after BLCL. Regional cerebral blood flow (r-CBF) in thalamus was also measured by the hydrogen clearance technique. The brain water content in the NIK-242inj. group was significantly lower than that of saline group. The concentration of brain ATP in the NIK-242inj. group remained higher than those of saline group. Accumulation of lactate in the NIK-242inj. group was less than in the mannitol and saline groups. The lactate/pyruvate ratio of the NIK-242 inj. group was significantly lower than that of the saline and mannitol groups. At 3h after BLCL, the reduction of r-CBF in the NIK-242inj. group was smaller than that of saline group. The present study suggests that NIK-242inj. as well as glycerol could ameliorate brain edema, disruption of brain energy metabolism and reduction of r-CBF in acutely induced cerebral ischemia.
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PMID:Effect of a new hyperosmotic agent, NIK-242 injection, on brain water content, metabolites and cerebral blood flow in cerebral ischemia in the spontaneously hypertensive rat. 176 86

Intracellular pH was determined by neutral red color histophotometry in cerebral tissue from rats subjected to 10 minutes of cardiac arrest and from rats that had recovered for 1 and 6 hours following 8-10 minutes of total cerebral ischemia (TIA). Tissue concentrations of ATP, lactate and glucose were measured corresponding to the pH determinations. As expected, tissue ATP was depleted while tissue lactate was markedly elevated after 10 minutes of ischemia without reflow in the cerebral cortex, striatum and hippocampus. However, both metabolites were near control following 1 and 6 hours of recovery in all three regions. Tissue glucose was not significantly different from control following 1 and 6 hours of reperfusion. During ischemia, the intracellular pH dropped to 6.5-6.7 in all three regions (p less than 0.05). But, since the initial pH of the hippocampus was 7.79 while that of the cerebral cortex and striatum was approximately 7.02, the net drop in pHi the hippocampus was greater than in the other two regions. Following 1 hour of reperfusion, a trend towards tissue alkalosis was observed in the cerebral cortex and striatum.
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PMID:Regional changes in intracellular pH determined by neutral red histophotometry and high energy metabolites during cardiac arrest and following resuscitation in the rat. 177 24

In vivo NMR (nuclear magnetic resonance) spectroscopy allows for non-invasive measurement of the intracellular pH and the concentration of different metabolites in defined areas of the brain. Phosphocreatine, ATP and lactic acid are of prime interest in ischaemia research. Moreover, a distinction can be made between glycolysis and the oxidative breakdown of glucose after administering C-13-labelled glucose. Finally, spectroscopy of fluorine-containing inert gases such as Freon-23 allows for measuring cerebral blood flow and for directly relating the metabolic alterations to the changes in cerebral blood flow. Given the non-invasive character of NMR spectroscopy all metabolic process occurring throughout one experiment can for the first time be followed up. Thus metabolic alterations during ischaemia can directly be correlated with post-ischaemic recovery processes. It has been shown with the cerebral ischaemia model in the cat that recovery after circulatory failure rather depends on post-ischaemic changes such as the recirculation rate or the speed of high-energy phosphate formation than on the speed of energy metabolism breakdown or acidosis occurring during ischaemia. The future of nuclear magnetic resonance spectroscopy in experimental ischaemia research certainly lies in the therapeutic range. As the exact extent of ischaemic damage can be determined in each experiment it is possible for the first time to define the effect of a drug substance on metabolic dysfunction in each individual experiment. This method is not only expected to reduce the number of laboratory animals but also to dramatically improve statistical variability compared to group comparisons.
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PMID:[Studies of experimental cerebral ischemia with NMR spectroscopy]. 185 98

Lactic acidosis has been proposed to be one factor promoting cell death following cerebral ischemia. We have previously demonstrated that cultured neurons and glial are killed by relatively brief (10 min) exposure to acidic solutions of pH less than 5 (Goldman et al., 1989). In the present series of experiments, we investigated the relationship between changes in intracellular pH (pHi) and cellular viability. pHi was measured using fluorescent pH probes and was manipulated by changing extracellular pH (pHe). Homeostatic mechanisms regulating pHi in neurons and glia were quickly overwhelmed: neither neurons nor glial cells were able to maintain baseline pHi when incubated at pHe below 6.8. Neuronal and glial death was a function of both the degree and the duration of intracellular acidification, such that the LD50 following timed exposure to HCl increased from pH, 3.5 for 10-min acid incubations to pHi 5.9 for 2-hr exposures and pHi 6.5 for 6-hr exposures. Replacement of HCl with lactic acid raised the LD50 to pHi 4.5 for 10-min acid exposures, but did not change the LD50 for longer exposures: pHi measurements concurrent with extracellular acidification suggested that the greater cytotoxicity of lactic acid relative to that of HCl was caused by the more rapid intracellular acidification associated with lactic acid. The onset of death after exposure to moderately acidic solutions was delayed in some cells, such that death of the entire cell population became evident only 48 hr after acid exposure. During this latency period, cellular viability indices and ATP levels fell in parallel.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acid-induced death in neurons and glia. 186 26

The ischemic threshold of protein synthesis and energy state was determined 1, 6, and 12 h after middle cerebral artery (MCA) occlusion in rats. Local blood flow and amino acid incorporation were measured by double tracer autoradiography, and local ATP content by substrate-induced bioluminescence. The various images were evaluated at the striatal level in cerebral cortex by scanning with a microdensitometer with 75 microns resolution. Each 75 x 75 microns digitized image pixel was then converted into the appropriate units of either protein synthesis, ATP content, or blood flow. The ischemic threshold was defined as the flow rate at which 50% of pixels exhibited complete metabolic suppression. One hour after MCA occlusion, the threshold of protein synthesis was 55.3 +/- 12.0 ml 100 g-1 min-1 and that of energy failure was 18.5 +/- 9.8 ml 100 g-1 min-1. After 6 and 12 h of MCA occlusion, the threshold of protein synthesis did not change (52.0 +/- 9.6 and 56.0 +/- 6.5 ml 100 g-1 min-1, respectively) but the threshold of energy failure increased significantly at 12 h following MCA occlusion to 31.9 +/- 9.7 ml 100 g-1 min-1 (p less than 0.05 compared to 1 h ATP threshold value; all values are mean +/- SD). In focal cerebral ischemia, therefore, the threshold of energy failure gradually approached that of protein synthesis. Our results suggest that with increasing duration of ischemia, survival of brain tissue is determined by the high threshold of persisting inhibition of protein synthesis and not by the much lower one of acute energy failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ischemic thresholds of cerebral protein synthesis and energy state following middle cerebral artery occlusion in rat. 187 7

We superimposed extreme hypercapnia (arterial Pco2 400-450 mmHg) immediately before and during incomplete cerebral ischemia to distinguish the role of intracellular pH (pHi) and bicarbonate [( HCO3-]i) in postischemic metabolic and electrophysiological recovery. Incomplete global ischemia was produced in seven anesthetized dogs by 30 min of intracranial hypertension followed by 4 h of reperfusion. ATP, phosphocreatine (PCr), and pHi were measured with 31P magnetic resonance spectroscopy, and [HCO3-]i was calculated from the Henderson-Hasselbalch equation using the measured pHi and sagittal sinus Pco2. Cerebral blood flow was reduced to 7 +/- 1 ml.min-1.100 g-1 (+/- SE) during ischemia with extreme hypercapnia, and pHi decreased to 5.72 +/- 0.09. During normocapnic reperfusion, pHi rapidly returned to near baseline values by 14 min. [HCO3-]i fell from 12.1 +/- 0.9 to 6.0 +/- 1.2 mM by the midpoint of ischemia and recovered by 30 min of reperfusion. ATP, PCr, and O2 consumption also recovered rapidly and completely. Somatosensory-evoked potentials (SEP) recovered to 43 +/- 10% of control amplitude. These results are in marked contrast to the poor metabolic and SEP recovery previously observed in hyperglycemic dogs in which pHi decreased to the same range as with hypercapnic ischemia, but in which [HCO3-]i was much lower (1.1 +/- 0.5 mM). Therefore, [HCO3-]i depletion during hyperglycemic ischemia may be a more important factor in recovery than end-ischemic pHi per se. We speculate that higher [HCO3-]i may improve glial cell buffering capacity or decrease iron availability for hydroxyl radical production.
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PMID:Bicarbonate conservation during incomplete cerebral ischemia with superimposed hypercapnia. 190 5

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