Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemia gives rise to severe energy depletion and influx of Ca from the extracellular space, and it is suggested that increased intracellular Ca leads to the activation of phospholipase C and A, and to liberation of free fatty acids (FFA) in particular arachidonic acid. Phenytoin has been reported not only to maintain the intra- and extracellular cation balance but blockade the Ca channel. The purpose of the present study is to investigate the effect of phenytoin on the liberation of FFA, energy metabolism and mononucleotide metabolism in ischemic brain. Male Wistar rats were subjected to global cerebral ischemia induced by the occlusion of basilar and bilateral common carotid arteries. The brains were frozen in situ by the funnel technique after 5 or 30 min of ischemia or after 10, 30, or 60 min of recirculation following 30 min of ischemia. Purine and pyrimidine nucleotides, FFA, and glycolytic intermediates were measured by HPLC, GLC, and fluoro-enzymatic method. In non-treated rats, ATP reached a nadir after 5 and 30 min of ischemia. Phenytoin significantly attenuated ATP depletion after 5 and 30 min of ischemia. And also E.C. is higher in phenytoin treated rats than in non-treated rats in ischemia. After 60 min of recirculation, ATP recovered to 1.93 +/- 0.02 mumol (72.3% of pre-ischemia) in treated rats but 1.60 +/- 0.07 mumol/g (60% of pre-ischemia) in non treated rats. In E.C., there are significant differences between non-treated and treated rats after 10 and 30 min of recirculation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[The effect of phenytoin on free fatty acid liberation and mononucleotide metabolism in transient ischemia]. 321 41

Following prolonged cerebral ischemia, primary electrophysiological recovery may be followed by secondary deterioration of the recovery process. It has been suggested that the secondary deterioration is caused by "late" cytotoxic brain edema. To test this hypothesis, adult normothermic cats were submitted to 1 h complete cerebral ischemia followed by 3 and 6 h recirculation, respectively. Postischemic recovery of energy metabolism was imaged by ATP-induced bioluminescence, and regional tissue pH and electrolyte content was measured in regions with and without metabolic recovery. In areas with postischemic restitution of metabolic activity, sodium gradually rose from 338 +/- 17 to 488 +/- 28 mumol/g protein and calcium from 8.81 +/- 0.35 to 18.24 +/- 0.97 mumol/g protein. Tissue potassium content decreased from 761 +/- 12 to 676 +/- 19 mumol/g protein and magnesium from 46.8 +/- 0.8 to 36.3 +/- 1.1 mumol/g protein. Tissue pH rose from 7.09 +/- 0.04 to 7.31 +/- 0.13 and 7.26 +/- 0.17 after 3 and 6 h recirculation, respectively. In areas without metabolic recovery, electrolyte disturbances were even more pronounced and pH--after transient alkalization--fell to 6.82 +/- 0.12. These data demonstrate that during the later phase of postischemic recirculation, progressive disturbances of electrolyte homeostasis create a preedematous situation that has to be considered for preventing delayed postischemic complications.
 ...
PMID:Regional pH and electrolyte homeostasis of cat brain after prolonged ischemia. 324 67

Dihydropyridine calcium channel blockers such as nicardipine are under evaluation for treating acute cerebral ischemia because they may increase cerebral blood flow by causing vasodilation and because they may be cytoprotective in part by limiting production of arachidonic acid metabolites. We demonstrated in a previous study that nicardipine improves postischemic neuronal function, as measured by somatosensory evoked potentials, without reducing the extent of light-microscopic CA-1 hippocampal histologic damage. To characterize further the effect of nicardipine on global ischemic injury, we administered the drug beginning 24 hours before 30 minutes of four-vessel ischemia in Wistar rats. We then measured hippocampal ATP, phosphocreatine, and glucose contents immediately and 2 hours after ischemia, and measured learning ability (working and reference errors) on an eight-arm radial maze beginning 30 days after ischemia. To gain insight into the possible mechanism of action, we measured production of arachidonic acid metabolites (eicosanoids: TXB2 and 6-keto-PGF1 alpha) and hemispheric and hippocampal cerebral blood flow by the [14C]butanol indicator fractionation technique immediately and 2 hours after ischemia. Nicardipine was associated with fewer working errors (p less than 0.02) but no difference in reference errors. The drug had no effect on energy metabolites, cerebral blood flow, or eicosanoids immediately after ischemia, but ATP, phosphocreatine, and cerebral blood flow all returned to normal levels significantly more rapidly during reperfusion in treated rats. Nicardipine improves behavioral, electrophysiologic, and mitochondrial function after ischemia without preventing cellular damage and improves postischemic reperfusion. The drug's positive effect appears to occur during reperfusion.
 ...
PMID:Efficacy and mechanism of action of a calcium channel blocker after global cerebral ischemia in rats. 336 73

Progressive cerebral ischemia was induced in seven anesthetized hyperglycemic rats by carotid artery ligation and hemorrhagic hypotension. Phosphorus metabolites, intracellular pH, and lactate in the brain were monitored by 31P and 1H magnetic resonance spectroscopy. Under conditions in which blood flow was low, phosphocreatine (PCr) concentration and intracellular pH decreased and the concentration of lactate increased. The decrease in ATP was approximately one-third that of PCr until only 25% PCr remained, after which ATP was lost more rapidly than PCr. These changes were interpreted in terms of three regions observed by the magnetic resonance coil, one of complete ischemia, one of partial ischemia, and one of perfusion sufficient to maintain normal metabolite levels. The extent of the three regions was estimated quantitatively. Broadening and splitting of the inorganic phosphorus (Pi) peak into two components provided further evidence of distinct populations of cells, one very acidic and another less so. Apparent intracellular buffering capacity was calculated as 23.6 +/- 1.3 mumol lactate/g wet wt/pH.
 ...
PMID:Metabolic changes during experimental cerebral ischemia in hyperglycemic rats, observed by 31P and 1H magnetic resonance spectroscopy. 336 94

Using two different models of non ischemic and transient cerebral ischemia in SHR, the effect of hyperosmolar solution with intravenous 10% glycerol on serum lipid peroxides, plasma prostaglandins (TXA2, PGI2), brain water content and brain metabolites were studied. Glycerol did not influence the levels of lipid peroxides, plasma prostaglandins and brain water content in the non ischemic rats. In the transient ischemia group, on the other hand, serum lipid peroxides were significantly reduced in the glycerol administrated group. On the study of plasma prostaglandins, there was no difference of TXA2 levels between two groups, but PGI2 levels were significantly increased in the glycerol administrated group. Brain water content was significantly decreased. And on the study of brain metabolites, ATP concentrations remained higher and lactate concentrations were lower in the glycerol administrated group compared with those in the control group. But there was no difference with pyruvate concentrations between two groups, furthermore L/P ratio improved in the glycerol administrated group. Besides the effect on reduction of brain edema as for hyperosmolar solution, glycerol may indicate improvement of ischemic impediments on brain by the action of antioxidation and reinforcement of PGI2.
 ...
PMID:[Effect of glycerol administration on experimental cerebral ischemia--Part 1. Studies on lipid peroxides, prostaglandins, brain edema and brain metabolites]. 337 Jan 71

Effects of indeloxazine hydrochloride [(+/-)-2-[(inden-7-yloxy)methyl]morpholine hydrochloride, YM-08054] on cerebral ischemia were investigated in animals. Indeloxazine prolonged the gasping duration dose-dependently in decapitated mice. Bilateral occlusion of the carotid artery for 5 min shortened the latency of step-through in passive avoidance task 4 days following ischemia in mongolian gerbils. The i.p. administration of indeloxazine was started just after the surgical operation and repeated twice a day for 4 days. Indeloxazine (2 mg/kg) significantly prolonged the latency of step-through in this amnesic model, indicating a reversal effect on the ischemia-induced amnesia. In biochemical studies, decreases in brain ATP and total adenine nucleotide levels were inhibited by indeloxazine (2 mg/kg i.p., once a day for 7 days) in four-vessel occluded rats. These findings indicate that indeloxazine possesses protective effects on cerebral ischemia presumably due, in part, to improvement of the cerebral energy metabolism.
 ...
PMID:Protective effects of indeloxazine hydrochloride on cerebral ischemia in animals. 344 40

The present study was designed to clarify the effect of brovincamine fumarate (BV 26-723: BV) on the degree of cerebral ischemia acutely induced by bilateral common carotid artery ligation (BLCL) in stroke-resistant spontaneously hypertensive rats (SHRSR). BV was administered to SHRSR by intraperitoneal infusion (I.P.) of 30 mg/kg (BV 30 mg/kg group), 60 mg/kg (BV 60 mg/kg group) and 0.9% saline was similarly injected to SHRSR (control group) before and immediately after BLCL. Cerebral blood flow (rCBF) in the thalamus was measured by hydrogen clearance technique before and until 3 hr of BLCL periodically. The brain metabolites (ATP, lactate, pyruvate) were determined by the enzymatic method and the brain water content was measured by freeze-dry method 3 hr after BLCL. The histopathological changes in brain vessels were observed by scanning electron microscopy (SEM) 3 hr after BLCL. The rCBF of three groups were identical before BLCL. However, the rCBF of BV 30 mg/kg group was statistically higher than in control group until 2 hr after BLCL, and that of BV 60 mg/kg group was significantly higher even 3 hr after BLCL. In measurements of the brain metabolites after BLCL, ATP and pyruvate levels in both the BV 30 mg/kg and 60 mg/kg groups were statistically higher than the control group. And brain lactate concentrations in both the BV 30 mg/kg and 60 mg/kg groups were significantly lower than the control group. The brain water content of BV 30 mg/kg and 60 mg/kg groups were significantly lower then the control group after BLCL.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Effect of brovincamine fumarate on cerebral ischemia acutely induced by BLCL in SHRSR]. 344 48

Glycerol, the end product of phospholipid degradation, was measured in cat brains under pathophysiological conditions known to cause activation of lipolysis, namely, bicuculline-induced seizures, permanent focal cerebral ischemia (2 hr of middle cerebral artery occlusion), and global cerebral ischemia (15 min of complete cerebral ischemia with or without 2 hr of recirculation). In addition, ATP and lactate were measured in order to correlate the activation of lipid degradation with disturbances in the energy-producing metabolism. A highly significant increase in the tissue glycerol content was observed after 1 hr of bicuculline-induced seizures (from 0.29 +/- 0.07 mumol/g in control animals to 1.30 +/- 0.06 mumol/g in seizure animals; P less than 0.001) or after 15 min of complete cerebral ischemia (from 0.29 +/- 0.07 to 1.17 +/- 0.14 mumol/g; P less than 0.01). Furthermore, a close correlation was found between the increase in glycerol and the increase in lactate or decrease in ATP after permanent focal ischemia. In contrast, following recirculation after complete cerebral ischemia, restoration of the energy pool did not lead to a reduction of the glycerol formed during ischemia. It is concluded that glycerol is a useful indicator of lipid degradation under pathological conditions. Since glycerol formed during vascular occlusion is trapped in brain cells, presumably owing to low glycerol kinase activity, it can be used as a stable postischemic indicator of ischemia-induced lipid degradation.
 ...
PMID:Glycerol as an indicator of lipid degradation in bicuculline-induced seizures and experimental cerebral ischemia. 350 34

Adult male gerbils were submitted to 5-minute cerebral ischemia by bilateral carotid artery occlusion. At the end of ischemia and at various recirculation times ranging from 15 to 120 minutes, brains were frozen in situ and the regional distribution of ATP, glucose, and tissue pH was studied on coronal cryostat sections by bioluminescent and fluoroscopic techniques. During ischemia ATP was completely depleted, glucose decreased to less than 10% of control, and regional tissue pH decreased from 7.04-7.09 to about 6.0. After the beginning of recirculation tissue pH and the regional content of metabolites exhibited a triphasic course. After 15 minutes pH returned to or even above normal, and ATP- and glucose-induced bioluminescence normalized. However, there was a secondary deterioration of both tissue acidosis and the metabolic state after 30 minutes. After longer recirculation times changes again improved and returned to normal within 2 hours. These changes were similar in all brain regions with the exception of the CA1 sector of the hippocampus, where the transient normalization of tissue pH was absent after 15 minutes of recirculation. This finding is in line with the previously observed microcirculatory insufficiency of this area and demonstrates that the CA1 sector of the hippocampus suffers more pronounced postischemic acidosis than other less vulnerable regions of the brain.
 ...
PMID:Effect of 5-minute ischemia on regional pH and energy state of the gerbil brain: relation to selective vulnerability of the hippocampus. 356 98

Nimodipine is known to improve postischemic cerebral blood flow (CBF) and neurologic outcome in experimental animals. Whether or not the two observations are related is unknown. This study searched for a possible improved rate of brain metabolic recovery in animals treated with nimodipine postischemia. Complete cerebral ischemia was produced for 11 min in 16 dogs, followed by reperfusion for 70 min. Prior to ischemia, glucose was administered (0.75 g X kg-1) in 12 dogs. Half of the glucose-treated dogs were given i.v. nimodipine, beginning 5 min postischemia (10 micrograms X kg-1 bolus followed by 1 microgram X kg-1 X min-1). The other half were given only saline postischemia. The remaining four dogs were given no glucose and received saline only postischemia. In all dogs, serial brain biopsies were taken at 2, 20, 40, and 70 min postischemia. In 5 dogs, the integrity of the blood-brain barrier (BBB) was tested by injection of Evans blue dye and postmortem examination of the brains. Brain biopsies were assayed for concentrations of phosphocreatine, ATP, ADP, AMP, glucose, lactate, and pyruvate. In all dogs, there was rapid restoration of a normal brain energy state following reperfusion. Brain lactate had returned to near normal in all dogs by 70 min postischemia, and the rate of lactate depletion was not different between groups. The integrity of the BBB was only minimally affected. A portion of the brain lactate was converted to pyruvate rather than crossing the BBB.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Nimodipine does not affect cerebral lactate levels following complete ischemia in dogs. 365 2


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>