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

The cerebral metabolic responses to perinatal hypoglycemia (blood glucose less than or equal to 1 mmol/l) combined with asphyxia were studied in paralyzed, lightly anesthetized newborn dogs. No major differences in heart rate, blood pressure or arterial acid-base balance between control and hypoglycemic animals occurred either prior to or during asphyxia. The electroencephalogram, unaltered by hypoglycermia alone, became isoelectric at the same intervals in both groups following respiratory arrest. Intravenous carbon black infusion at 5 min of asphyxia demonstrated no relationship between blood glucose level and cerebral perfusion (p > 0.05), whereas a positive correlation did exist between systemic blood pressure and cerebral perfusion (p < 0.01). During asphyxia, anaerobic glycolysis in brain was less enhanced in hypoglycemic dogs, resulting in a more rapid exhaustion of high-energy phosphate reserves (phosphocreatine, ATP and ADP). Thus, the cerebral metabolic responses to asphyxia superimposed upon hypoglycemia were the direct consequence of insufficient cerebral glucose stores coupled with deficient circulating glucose to brain. These metabolic disturbances were no more the result of cerebral ischemia than that which occurs during asphyxia alone. The findings also suggest that systemic physiological monitoring may be an inadequate means of appraising cerebral homeostasis during combined hypoglycemia ad hypoxia.
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PMID:Cerebral metabolism during hypoglycemia dn asphyxia in newborn dogs. 689 22

Hypothermia results in a progressive depression of cerebral electrical activity and metabolism. In the setting of cerebral ischemia, large reductions in temperature are associated with a better preservation of high-energy phosphates, a reduced accumulation of toxic metabolites, and an improvement in post-ischemic outcome. With temperature reductions of < or = 6 degrees C, the brain is also partially protected from ischemic neurologic injury; however, this protection does not correlate with measurable alterations in high-energy phosphate depletion or lactate accumulation. Thus, cerebral protection by hypothermia may be due to a variety of factors, including alterations in basal metabolism, ion homeostasis, agonist-specific receptor activity, and cellular structure. Further, the relative influence of these factors may change with progressive reductions in temperature.
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PMID:Cerebral metabolic rate and hypothermia: their relationship with ischemic neurologic injury. 754 75

Evidence suggests that ischemic neuronal necrosis may ultimately be the result of excessive intracellular calcium accumulation. In principle, abnormal calcium concentrations during ischemia are derived from three main sources: exaggerated influx via (a) voltage-operated channels, (b) receptor-controlled channels (f. ex. NMDA) and (c) the release of intracellular calcium ion stores. Previous studies using either calcium channel blockers or NMDA antagonists have demonstrated only limited protective effects of these agents in global transient cerebral ischemia, whereas little or no attention has been paid to the calcium sources listed under (c). Dantrolene has been shown to block the increase in free intracellular calcium ion stimulated by either NMDA or glutamate. Thus we postulated that dantrolene might improve neuronal survival in vulnerable regions to ischemia such as the CA1 hippocampus. Male Sprague-Dawley rats (300 approximately 400 g) were prepared for a four-vessel occlusion model of cerebral ischemia. Complete cerebral ischemia was induced by snaring the carotid arteries for 15 mins and maintaining mean arterial pressure at 80 mmHg. Strict attention was paid to keep normal blood gas values. Following ischemia halothane anesthesia was discontinued, and rats were extubated and when stable transferred to cages with free access to water and food. Rats survived for 7 days under close supervision, after which they were anesthetized with pentobarbital and perfused transcardially with 4% paraformaldehyde/sodium-phosphate buffer. The brain was removed and placed in fresh fixatives for another 7 days, after which 40 microns sections were cut and silver-stained.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of dantrolene on histological and behavioral outcome in rat CA1 hippocampus after global transient cerebral ischemia]. 769 30

The effects of cerebral ischemia on calcium/calmodulin-dependent kinase II (CaM kinase II) were investigated using the rat four-vessel occlusion model. In agreement with previous results using rat or gerbil models of cerebral ischemia or a rabbit model of spinal cord ischemia, this report demonstrates that transient forebrain ischemia leads to a reduction in CaM kinase II activity within 5 min of occlusion onset. Loss of activity from the cytosol fractions of homogenates from the neocortex, striatum, and hippocampus correlated with a decrease in the amount of CaM kinase alpha and beta isoforms detected by immunoblotting. In contrast, there was an apparent increase in the amount of CaM kinase alpha and beta in the particulate fractions. The decrease in the amount of CaM kinase isoforms from the cytosol but not the particulate fractions was confirmed by autophosphorylation of CaM kinase II after denaturation and renaturation in situ of the blotted proteins. These results indicate that ischemia causes a rapid inhibition of CaM kinase II activity and a change in the partitioning of the enzyme between the cytosol and particulate fractions. CaM kinase II is a multifunctional protein kinase, and the loss of activity may play a critical role in initiating the changes leading to ischemia-induced cell death. To identify a structural basis for the decrease in enzyme activity, tryptic peptide maps of CaM kinase II phosphorylated in vitro were compared. Phosphopeptide maps of CaM kinase alpha from particulate fractions of control and ischemic samples revealed not only reduced incorporation of phosphate into the protein but also the absence of a limited number of peptides in the ischemic samples. This suggested that certain sites are inaccessible, possibly due to a conformational change, a covalent modification of CaM kinase II, or steric hindrance by an associated molecule. Verifying one of these possibilities should help to elucidate the mechanism of ischemia-induced modulation of CaM kinase II.
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PMID:Effect of cerebral ischemia on calcium/calmodulin-dependent protein kinase II activity and phosphorylation. 771 3

Based on evidence for a direct central mechanism of insulin action in mitigating damage due to cerebral ischaemia, we have recently shown that centrally administered insulin, and to a lesser extent, insulin-like growth factor-1 (IGF-1), reduce ischaemic damage in fed rats. Because a portion of the neuroprotective effect of insulin may be due to peripheral hypoglycaemia, we undertook the present series of experiments to determine whether insulin or IGF-1 are neuroprotective in fasted rats, which already have low blood glucose values. Continuous minipump delivery of insulin (1 IU rat-1 day-1 n = 13), or IGF-1 (50 micrograms rat-1 day-1 n = 10) was compared to control rats treated with phosphate buffered saline (PBS 25 microliters rat-1 day-1 n = 10). Quantitative neuropathology was done one week after 10 min and 15 sec of transient forebrain ischaemia induced by bilateral carotid artery clamping at a mean arterial BP (MABP) of 50 mmHg. In all areas examined i.e. neocortex, striatum, and hippocampus, the three groups showed similar degrees of necrosis (p > 0.05), although there were insignificant trends for a beneficial effect of insulin in reducing selective neuronal necrosis in hippocampus. The results, in combination with previous studies, indicate that insulin is more effective in attenuating brain damage in fed rats.
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PMID:Centrally administered insulin and IGF-1 in transient forebrain ischaemia in fasted rats. 791 95

Effect of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1- benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1, CAS 127061-56-7), a diester of alpha-tocopherol and ascorbic acid, on transient cerebral ischemia was studied in Mongolian gerbils. Cerebral energy metabolism and intracellular pH (pHi) were estimated employing in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Intraperitoneal injection of EPC-K1 (5 or 10 mg/kg) prior to ischemia significantly ameliorated pHi reduction in a dose dependent manner during ischemia. After reperfusion, energy and pHi recoveries were significantly faster in the EPC-K1 groups than in the control group. EPC-K1 (10 mg/kg) significantly reduced the extent of cerebral edema. Moreover, administration of EPC-K1 immediately after reperfusion significantly shortened the consciousness recovery in a dose dependent manner. The results suggest that EPC-K1 may exert protective effects on ischemic brain and may have therapeutic value in ischemic stroke.
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PMID:Effects of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1- benzopyran-6yl-hydrogen phosphate] potassium salt on cerebral energy state and consciousness recovery following transient forebrain ischemia in gerbils. 798 54

The effects of acetyl-L-carnitine (ALCAR) treatment on brain energy state recovery and lactic acid levels following 20 min ischemia and 2, 24 and 48 h reperfusion were investigated by 31P and 1H-NMR spectroscopy. Transient forebrain ischemia was induced by four-vessel occlusion method in fed 6-month-old Fischer rats. ALCAR or saline was administered by intraperitoneal route immediately after 20 min ischemia and again at 1, 4, 24 and 30 h during reperfusion. Twenty-min severe forebrain ischemia was associated with a marked decrease in phosphocreatine (PCr) and ATP levels and a corresponding increase in lactic acid, inorganic phosphate (Pi), AMP, creatine, glycerol 3-phosphate and alanine levels. Following reperfusion, a general tendency to restore pre-ischemic metabolite levels was observed. However, after 2 h reperfusion in saline-treated rats, lactic acid and Pi levels remained significantly higher, while ATP levels were still significantly lower than in non-ischemic controls. On the contrary, in ALCAR-treated animals a complete recovery of all metabolites including Pi and ATP was observed, while PCr levels were even more elevated compared with those in saline-treated rats. Furthermore lactic acid content was significantly lower than that in both saline-treated and non-ischemic control rats. It is concluded that a potential therapeutic role may be claimed for ALCAR in the treatment of cerebral ischemia through mechanisms that include faster recovery and improvement of brain energy production as well as a decreased lactic acid content during early post-ischemic reperfusion.
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PMID:Effect of acetyl-L-carnitine on recovery of brain phosphorus metabolites and lactic acid level during reperfusion after cerebral ischemia in the rat--study by 13P- and 1H-NMR spectroscopy. 803 36

A beneficial effect of insulin in reducing cerebral ischemic damage has been recently demonstrated, and a direct central mechanism of insulin action in cerebral ischemia has been proposed. To test the hypothesis that one of the neuroprotective mechanisms of insulin action involves a direct interaction with CNS tissue via a growth factor effect, a continuous intraventricular infusion of two doses of insulin and of insulin-like growth factor 1 (IGF-1) was given to fed Wistar rats subjected to 10 min, 15 s of transient forebrain ischemia. Quantitative neuropathology after 1-week survival showed that low-dose insulin (7 IU/rat/day; n = 10) reduced selective necrosis in the striatum (p = 0.015) and one level of the hippocampus (p = 0.023) as compared with animals infused with phosphate-buffered saline (200 microliters/rat/day; n = 8). IGF-1 (50 micrograms/rat/day; n = 8) significantly ameliorated hippocampal damage in four of the six hippocampal levels (p < 0.05). High-dose insulin infusion (23 IU/rat/day; n = 8) produced a robust reduction in cortical (p = 0.0108), striatal (p = 0.003), and hippocampal (p < 0.05) necrosis at all coronal levels. However, this high-dose insulin reduced the blood sugar significantly (p < 0.01), from 11.8 to 7.8 mM, probably by virtue of centrally administered insulin reaching the periphery. We conclude that insulin and IGF-1 offer a moderate, centrally mediated, neuroprotective effect, likely mediated at least in part via a growth factor mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraventricular administration of insulin and IGF-1 in transient forebrain ischemia. 811 20

A research program in cerebral ischemia was initiated by our laboratory to determine optimal strategies for cerebroprotection. Four studies relating to cerebroprotection using nuclear magnetic resonance spectroscopy in a sheep model of hypothermic cardiopulmonary bypass are summarized. These showed, first, that low-flow bypass, with a flow as low as 10 mL.kg-1 x min-1, maintained normal cerebral metabolism; second, that hypothermia increases the high-energy phosphate content and the intracellular pH of the brain; third, that hyperglycemia causes a profound intracellular acidosis; and, finally, that barbiturates prevent the normal increase in high-energy phosphates associated with hypothermia.
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PMID:Low-flow cardiopulmonary bypass and cerebral protection: a summary of investigations. 826 75

We used 31P magnetic resonance spectroscopy (MRS) to investigate changes in brain intracellular [Mg2+] following human focal cerebral ischemia. Mean brain pMg (where pMg = -log[Mg2+]) was significantly lower in the ischemic focus of all stroke patients (pMg = 3.34 +/- 0.28, n = 45, p < 0.01) when compared with normal controls (pMg = 3.50 +/- 0.08, n = 25). Ischemic brain pMg was also significantly reduced when the pH of the stroke region was acidotic (pH < 6.90, pMg = 3.07 +/- 0.44, n = 11, p < 0.01) and when the phosphocreatine index (PCrI = PCr/[PCr+Pi (inorganic phosphate)]) was reduced (PCrI < 0.47, pMg = 3.12 +/- 0.42, n = 13, p < 0.01). Mean brain pMg was significantly reduced at days 0 to 1 (acute) poststroke (pMg = 3.32 +/- 0.28, n = 26, p < 0.01) and at days 2 to 3 (subacute) poststroke (pMg = 3.38 +/- 0.28, n = 21, p = 0.03). There was also a significant (p < 0.01) correlation between decreased pMg and increased relative signal intensity of Pi (normalized by total phosphate signal, Pi/TP) for all stroke groups studied. During the temporal evolution of stroke, pH returned to normal levels by days 2 to 3, and pMg returned to normal by days 4 to 10 (subacute). PCrI and Pi/TP returned toward normal levels after 10 days (chronic), at a time when ischemic brain pH had become significantly alkalotic (pH = 7.10 +/- 0.24, n = 15, p < 0.01). Elevation of ischemic brain [Mg2+] is temporally linked to the acidotic phase of human stroke as well as the breakdown of energy metabolism. These acute changes in [Mg2+] may contribute to, or be a marker for, cellular injury.
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PMID:Acute elevation and recovery of intracellular [Mg2+] following human focal cerebral ischemia. 835 Oct 15


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