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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alterations of the second-messenger systems, adenylate cyclase (AC) and protein kinase C (PKC), and local cerebral blood flow (lCBF) were evaluated during experimental cerebral ischemia in gerbils employing a quantitative autoradiographic method, which permitted these three parameters to be measured in the same brain. Ischemia was induced by occlusion of the right common carotid artery for 6 h. Animals attaining more than 5 in their ischemic scores were utilized for further experiments. At the end of ischemia, lCBF was measured by the [14C]iodoantipyrine method. The AC and PKC activities were estimated by the autoradiographic technique developed in our laboratory using [3H]forskolin (FK) and [3H]phorbol-12,13-dibutyrate (PDBu), respectively. The lCBF fell below 10 ml/100 g/min in most cerebral regions on the ligated side. The greatest reduction in FK binding was noted in the olfactory tubercle, caudate-putamen, and globus pallidus, followed by the hippocampus and cerebral cortices. The FK binding tended to be low at lCBF less than 20 ml/100 g/min in the cerebral cortices. However, the PDBu binding was relatively well preserved in each cerebral structure, and no significant correlation between lCBF and PDBu binding was noted in the cerebral cortices. The AC system may thus be vulnerable to ischemic insult over extensive brain regions, while the PKC system may be relatively resistant to ischemia.
J Cereb Blood Flow Metab 1991 Mar
PMID:Autoradiographic analysis on second-messenger systems and local cerebral blood flow in ischemic gerbil brain. 199 99

Twenty-four hour postischemic neuronal necrosis was compared in male vs. female Mongolian gerbils subjected to a 3-h period of severe incomplete hemispheric ischemia produced by unilateral carotid occlusion. The incidence of stroke-prone males was 42.9% versus 26.7% for the females. Among the stroke-prone animals, the males displayed significantly greater neuronal necrosis at 24 h after ischemia compared to the females in the cerebral cortex and CA1 region of the hippocampus. In the CA1 region of the stroke-prone males, only 2.0% of the normal neuronal population remained by 24 h compared to 36.8% in the stroke-prone females (p less than 0.02). In the cerebral cortex, the males had only 19.9% of normal versus 58.2% in the females (p less than 0.05). In a second series of mechanistic experiments, no differences in cortical blood flow (CBF) were disclosed between preselected male and female stroke-prone animals before, during, or for 2 h after ischemia. As with the CBF, the extent of cortical extracellular hypocalcia during ischemia did not differ significantly. However, the degree of postischemic recovery of cortical extracellular calcium was significantly better in the females from 30 min to 2 h after reperfusion. In the same experiments, hemispheric vitamin E levels were measured at the 2 h time point as an index of postischemic brain lipid peroxidation. No difference in baseline vitamin E levels was observed between male and female sham-operated gerbils. In the males subjected to 3 h of ischemia plus 2 h of reperfusion, the hemispheric vitamin E decreased by 43.5% compared to the sham-operated males.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cereb Blood Flow Metab 1991 Mar
PMID:Sex differences in postischemic neuronal necrosis in gerbils. 199

Brief ischemia induced tolerance to subsequent ischemia in the hippocampal neurons. Male Mongolian gerbils were subjected to 2 min of ischemia in an awake condition. This ischemic insult only rarely produced neuronal damage in the gerbil brain. One day (n = 9), 2 days (n = 9), or 4 days (n = 10) following the first brief ischemia, the animals (double-ischemia group) were subjected to the second ischemia for 5 min. The single-ischemia group received a sham procedure instead of the first ischemia and was identically subjected to the second ischemia 1 day (n = 9), 2 days (n = 10), and 4 days (n = 13) following the sham procedure. One week following the second ischemia, all gerbils were perfusion fixed and the neuronal density in the hippocampal CA1 sector was measured. In double-ischemia groups, the neuronal density per 1-mm length of the pyramidal cell layer was 103.4 +/- 93.1 (SD) in the 1-day subgroup, 125.6 +/- 64.2 in the 2-day subgroup, and 176.2 +/- 93.7 in the 4-day subgroup, while the density in normal gerbils was 254.7 +/- 18.6. The average neuronal density in the single-ischemia group was much lower than that in the double-ischemia group (whole control group: 10.9 +/- 27.4). Immunostaining using monoclonal antibody raised against 70-kDa heat-shock protein revealed an increase in 70-kDa heat-shock protein in the CA1 area following 2 min of ischemia. Very brief ischemia induces heat-shock proteins and, presumably, thereby renders neurons more tolerant to subsequent metabolic stress.
J Cereb Blood Flow Metab 1991 Mar
PMID:Induced tolerance to ischemia in gerbil hippocampal neurons. 199 1

Free choline and ATP contents were measured in Mongolian gerbil hippocampal slices (tissue) and incubation media (media) during exposure to 30 min of aglycemia, high potassium, anoxia, or ischemia. Changes in choline levels reflected the degree of energy reduction, lower ATP levels being associated with high choline (4-fold increase during exposure to high potassium and anoxia, and 11-fold increase during ischemia). Media (extracellular) choline was particularly affected and increased about twofold during relatively mild energy depletion (e.g., aglycemia), but tissue choline content was less sensitive to energy reduction. A plot of choline vs. ATP levels indicated a nonlinear correlation, and the sharp increase in choline occurred when ATP values fell to about 2.5 nmol/mg of protein. Inhibition of acetylcholine sterase by 10 microM physostigmine during ischemia did not prevent an increase in choline contents but rather enhanced them, indicating that acetylcholine hydrolysis was not the source of free choline. Formation of free choline was Ca2+ independent. These findings suggest the involvement of phospholipase D and phosphatidylcholine hydrolysis in free choline formation during energy stress. The extent of choline formation may be an indicator of the degree of membranal damage, which in turn reflects damage to the metabolic machinery of the cell.
J Cereb Blood Flow Metab 1991 Mar
PMID:Formation of free choline in brain tissue during in vitro energy deprivation. 199 2

Brain slices of varying thickness were used to modify retention of metabolic products in an in vitro model of ischemia. Past and present results reveal increased anaerobic glycolysis in 660-microns slices with accumulation of lactate as slice thickness reaches 1,000 microns. Brain slice glucose utilization and lactate content were measured in buffers of various extracellular K+ levels and pH in 540-, 660-, and 1,000-microns slices. Acidosis suppresses glucose utilization at all slice thicknesses without affecting tissue lactate. Studies of 2-deoxyglucose metabolites establish that the suppression of glucose utilization by acidosis is due entirely to inhibition of glucose phosphorylation without any effect on glucose uptake into tissue. The inhibition is reversible after 45 min at pH 6.1. The experiments with acidosis also suggest that persistent energy demands continue to stimulate phosphofructokinase despite the low pH so that glycolysis continues, with potential for injury. Increasing K+ increases glucose utilization and tissue lactate at all three thicknesses. Correlations of glucose utilization with lactate accumulation support the possibility that high K+ may exert a dual influence on the tissue metabolism, not only stimulating glucose utilization by inducing depolarization but also by influencing the removal of metabolic products.
J Cereb Blood Flow Metab 1991 May
PMID:Ischemic brain slice glucose utilization: effects of slice thickness, acidosis, and K+. 201 47

The early time period following ischemia may be of pathogenetic importance in hypoxic-ischemic brain injury. Global cerebral oligemia was induced in ten late gestation fetal sheep by inflation of a balloon occluder around the brachiocephalic artery. Cerebral blood flow, oxygen, glucose, and lactate net flux, and oxygen delivery were measured by the Fick principle following 1 h of oligemia and at 5, 30, and 60 min of postoligemic reperfusion. During oligemia, cerebral blood flow decreased by 74 +/- 10% (mean +/- SD) and oxygen consumption decreased by 34 +/- 24%. The glucose:oxygen quotient was elevated throughout the oligemic period. In the early (5 min) reperfusion period, blood flow and oxygen delivery were not different from control but oxygen consumption was persistently depressed by 27 +/- 32%; fractional extraction of oxygen was 0.38 +/- 0.10 during control and 0.24 +/- 0.09 during early reperfusion. The venous oxygen tension increased modestly from 15.2 +/- 2.4 to 18.0 +/- 1.7 mm Hg; the postoligemic venous pO2 was limited by the lack of reactive hyperemia combined with the low arterial pO2 of the intrauterine environment. Postoligemic carbohydrate fluxes could not be differentiated from control possibly due to blood-brain barrier limitations. These factors may be related to the relative resistance of the fetal brain to hypoxic-ischemic injury.
J Cereb Blood Flow Metab 1991 May
PMID:Fetal cerebral blood flow and metabolism during oligemia and early postoligemic reperfusion. 201 48

Induction of mRNA encoding the 70 kDa stress/heat shock protein, hsp70, was evaluated in post-ischemic gerbil brain by in situ hybridization using an oligonucleotide probe selective for stress-inducible members of this gene family. Expression of hsp70 sequences was most pronounced in hippocampal CA1 neurons that fail to accumulate immunoreactive hsp70 protein, and that are selectively lost following ischemia. Hybridizable RNA continued to be expressed in CA1 through at least 48 h, essentially until the onset of cell death in this model. In contrast, dentate granule cells and CA2 neurons destined to survive the insult showed transient induction of hsp70 mRNA during the first 24 h of recirculation that disappeared prior to the detection of maximal hsp70 immunoreactivity in these cell populations. Pretreatment with a single injection of MK-801 (10 mg/kg) considerably attenuated the induction of hsp70 mRNA in hippocampus at 6 h of recirculation, an effect apparently mediated by persistent drug-induced hypothermia. The drug did not prevent the later, selective appearance of hsp70 hybridization in CA1 neurons at 24 h, nor did it protect against the subsequent loss of these cells. These results demonstrate a prolonged postischemic stress response at the transcriptional level in vulnerable hippocampal neurons, and suggest its utility as a marker for neuronal pathophysiology associated with mechanisms mediating delayed neuronal death.
J Cereb Blood Flow Metab 1991 May
PMID:Localization of 70 kDa stress protein mRNA induction in gerbil brain after ischemia. 201 50

The bilateral carotid occlusion model and a polyclonal antibody to the carboxyl terminus of the rat brain/human hepatoma glucose transporter were used to examine quantitatively changes in the transporter in gerbil hippocampal microvessels following 6-7.5 min of ischemia. The optical densities of immunocytochemically stained microvessels in the stratum lacunosum-moleculare (SLM) below the CA1 subfield were determined using image analysis of frozen sections from gerbils killed 2 h, 3 days, 6 days, 4 weeks, and 7 weeks after the ischemic episode. Microvessels were sparsely distributed in the stratum oriens, stratum pyramidale, and stratum radiatum. In contrast, the SLM was relatively well vascularized, and this distribution of microvessels persisted following ischemia. The SLM was identifiable based solely on microvessel distribution both in control gerbils and in gerbils that exhibited complete destruction of CA1 pyramidal cells. The abundance of the glucose transporter in SLM microvessels remained constant, suggesting that down-regulation of this protein cannot account for reported declines in brain glucose utilization and cell death following ischemia. Conversely, the presence and metabolic activity of CA1 pyramidal cells do not appear to be determinants of glucose transporter abundance in hippocampal microvessels. The brain/hepatoma glucose transporter was abundant in brain microvessels and the epithelial cells of the choroid plexus of gerbil and rat. Staining of hippocampal neuropil was less intense, poorly localized, and, at the light microscope level, not clearly associated with a particular cell type.
J Cereb Blood Flow Metab 1991 May
PMID:Quantitative immunocytochemistry (image analysis) of glucose transporters in the normal and postischemic rodent hippocampus. 201 51

We investigated the effect of hyperthermic pretreatment before induction of ischemia using a gerbil model of 5-min forebrain ischemia. A single hyperthermic treatment 18 h before ischemia exhibited a partial protective effect, and repetitive hyperthermic pretreatments at 18-h intervals before ischemia showed clear protection against neuronal death in the CA1 area of the hippocampus, whereas single hyperthermic treatment 3, 6, 24, or 50 h before ischemia exhibited little protective effect. This transient and cumulative neuroprotective effect of hyperthermic pretreatment strongly suggested the involvement of stress reactions after hyperthermia in the protective mechanism against ischemic neuronal death.
J Cereb Blood Flow Metab 1991 May
PMID:Hyperthermia-induced neuronal protection against ischemic injury in gerbils. 201 52

The metabolic effects of R-phenylisopropyladenosine (R-PIA), an agonist of adenosine A1 receptors, were studied by in vivo 31P NMR spectroscopy before, during, and after 30 min of reversible forebrain ischemia in the rat. R-PIA had no effect on cerebral metabolism before ischemia. During a 30-min ischemia, R-PIA reduced the decrease in phosphocreatine (43 +/- 11% of the control level at the end of ischemia vs. 27 +/- 9% in the reference group) and ATP (58 +/- 12% vs. 40 +/- 23%) and the increase in inorganic phosphate (672 +/- 210% vs. 905 +/- 229%). The intracellular acidosis elicited by ischemia was also less in the treated group (pH of 6.40 +/- 0.10 vs. 6.30 +/- 0.10). Recirculation was associated with a faster recovery of PCr, ATP, Pi, and pHi to control levels in the treated group than in the reference group. It is concluded that adenosine protects against ischemic injury by mechanisms that include metabolic protection.
J Cereb Blood Flow Metab 1991 May
PMID:Metabolic effects of R-phenylisopropyladenosine during reversible forebrain ischemia studied by in vivo 31P nuclear magnetic resonance spectroscopy. 201 53


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