Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The removal of glutamatergic afferents to CA1 by destruction of the CA3 region is known to protect CA1 pyramidal cells against 10 min of transient global ischemia. To investigate further the pathogenetic significance of glutamate, we measured the release of glutamate in intact and CA3-lesioned CA1 hippocampal tissue. In intact CA1 hippocampal tissue, glutamate increased sixfold during ischemia; in the CA3-lesioned CA1 region, however, glutamate only increased 1.4-fold during ischemia. To assess the neurotoxic potential of the ischemia-induced release of glutamate, we injected the same concentration of glutamate into the CA1 region as is released during ischemia in normal, CA3-lesioned, and ischemic CA1 tissue. We found that this particular concentration of glutamate was sufficient to destroy CA1 pyramids in the vicinity of the injection site in intact and CA3-lesioned CA1 tissue when administered during control (non-ischemic) conditions. In contrast, the same amount injected during ischemia in the CA3-lesioned CA1 region destroyed pyramidal cells in a widely distributed zone around the injection site in the CA1 region. It is concluded that the ischemia-induced damage of pyramidal cells in CA1 is dependent on glutamate release and intact innervation from CA3.
 ...
PMID:Ischemic damage in hippocampal CA1 is dependent on glutamate release and intact innervation from CA3. 257 Jul 85

The influence of transient forebrain ischemia on the temporal alteration of protein kinase C (PKC) activity in the rat hippocampus was analyzed by quantitative autoradiography using [3H]phorbol 12,13-dibutyrate [( 3H]PDBu). As reported previously, the grain density was highest in the strata oriens and radiatum in the CA1 subfield. After transient forebrain ischemia (20 min), the [3H]PDBu binding in the CA1 subfield gradually increased during early recirculation, and became maximum 6-12 h after ischemia, when no microscopic damage of the CA1 pyramidal cells was obvious. Thereafter, grain density decreased and binding activity in the CA1 was lost by approximately 40% 7 days after ischemia, when CA1 pyramidal cells had become necrotic. This indicated a close association of phorbol ester binding sites with CA1 pyramidal cells. By contrast, [3H]PDBu binding sites were unchanged in the stratum radiatum in the CA3 throughout the recirculation, although the number of binding sites in the stratum oriens of the CA3 was decreased during early recirculation period. Seven days after recirculation, in the molecular layer of the dentate gyrus, where granule cells remained intact, [3H]PDBu binding activity increased by 33%, with a higher grain density in the inner region (supragranular layer). These results suggest that enhancement of PKC activity and/or translocation of the enzyme play an important role in the postischemic modulation of synaptic efficacy in the hippocampal formation and neuronal death of CA1 pyramidal cells.
 ...
PMID:Protein kinase C activity in the rat hippocampus after forebrain ischemia: autoradiographic analysis by [3H]phorbol 12,13-dibutyrate. 270 52

Hippocampal brain slices that were 1000 mu thick were prepared from Sprague-Dawley rats and studied using in vitro glucose utilization under well-oxygenated conditions or after a 15 min anoxic insult produced with a nitrogen atmosphere. Autoradiography reveals that glucose utilization is increased in CA1 and CA3 stratum radiatum of 1000 mu slices, even with full oxygenation, compared to the same regions in 540 mu slices. Following anoxia, there is an initial addition increase in stratum oriens of CA1 and CA3 glucose utilization that is followed by a decline in glucose utilization in all slice regions within an hour of the insult. Because increased glucose utilization is apparent at the slice surfaces as well as at the interior, it is suggested that thick brain slices are a model of brain ischemia, not just hypoxia.
 ...
PMID:Glucose utilization of ischemic hippocampal slices. 272 13

The effects of the calcium entry blocker emopamil on physiological variables, local cerebral blood flow (LCBF) and on hippocampal cell damage were evaluated after 10 min of forebrain ischemia in the rat. LCBF was determined with the 14C-iodoantipyrine technique after 2, 10, and 60 min of postischemic recirculation. Histological evaluation was performed 7 days after ischemia in cortical and hippocampal tissue by determination of the percentage of necrotic neurons. Preischemic application of emopamil [4 mg/kg racemate or 2 mg/kg (S)-emopamil; i.v.] caused increased in LCBF in cortical areas but did not alter blood flow in the hippocampus at 2 min of recirculation. After 10 and 30 min of flow resumption no differences in LCBF between drug-treated and control animals were observed. In the histological series (S)-emopamil was applied at doses of 2, 4 or 6 mg/kg before the induction of ischemia. After 7 days of postischemic recovery, neuronal damage was significantly reduced by the calcium antagonist in hippocampal CA1 sector at all doses tested, the most prominent effects being observed with the lowest dose. At this dose cell loss in the CA3 sector was also reduced. In cortical tissue the number of necrotic cells remained unchanged by emopamil treatment. It is concluded that the calcium antagonist emopamil can reduce ischemia-induced neuronal cell damage. The compound improves circulation in cortical tissue only during early recovery but not at later phases of reflow, i.e. the period of delayed hypoperfusion. These increases in blood flow are not of crucial importance for ultimate neuronal death in this area.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of emopamil on postischemic blood flow and neuronal damage in rat brain. 272 98

Autoradiographic imaging demonstrated predominant and reciprocal localization of forskolin and inositol 1,4,5-trisphosphate (IP3) binding sites in synaptic areas in the hippocampus. We produced selective damage to the CA1 pyramidal cells in the rat hippocampus by means of transient forebrain ischemia and analyzed the alteration of the intracellular signal transduction using quantitative autoradiography of these second messenger systems. The dendritic fields (stratum oriens, radiatum and lacunosummoleculare) in the CA1 showed 20% decrease in [3H]IP3 binding activity 3 h after ischemia, when no morphological abnormalities were obvious. Thereafter, grain density in these layers decreased and half of the binding sites were lost 2 days after ischemia. By contrast, the stratum pyramidale of the CA1 showed no significant change until 2 days after recirculation. Seven days after ischemia, when CA1 pyramidal cells were depleted, all layers in the CA1 subfield lost 85% of [3H]IP3 binding sites. In the CA3 subfield, only a small and transient alteration in the [3H]IP3 binding was noticed during recirculation. Postischemic reduction of [3H]forskolin binding sites was obvious in the CA1 only 1 h after ischemia followed by loss of 50% of binding activity 7 days after recirculation. These results suggest that forskolin and IP3 binding sites are predominantly distributed on the pyramidal cells in the CA1 subfield and that marked alteration of intracellular signal transduction precedes the delayed CA1 pyramidal cell death.
 ...
PMID:Mapping second messenger systems in the rat hippocampus after transient forebrain ischemia: in vitro [3H]forskolin and [3H]inositol 1,4,5-trisphosphate binding. 278 45

To elucidate mechanisms of intra-and postischemic brain damage, regional alterations of calcium and energy metabolism were investigated by histochemical methods. Permanent ischemia of 1 and 3 hours, and temporary ischemia of 15 min, 1 and 3 hours with subsequent recirculation were made in gerbils. In the first of present study, calcium leakage was studied in the permanent ischemia. Abnormal calcium stains were observed in the area where ATP content markedly decreased, and they were already noted in the 15 min ischemia. These calcium stains were mainly seen around the blood vessels, and also seen in the tissue at the border of the ischemic area. Distribution of the calcium stains were more intense in the proximity of the large arteries than their distal portion. Thus the results show calcium leakage from the blood vessels developed in the early stage of ischemia, and such vessels were localized in the area where decrease of perfusion pressure was persisted above the level sufficient for calcium leakage. In the second of present study, regional changes of calcium and energy metabolism were studied in reperfusion of 1 and 3 hours hemispheric ischemia. Although postischemic restoration of brain ATP content varied greatly in different regions, the ATP restoration after the 1 hour ischemia was better than that after the 3 hours ischemia. Abnormal calcium stains were seen in the cortex, the hippocampal Ammon's horn, the ventral postero-lateral thalamic nucleus and the habenula. These calcium stains mainly localized in the neurons, which were different from intraischemic ones. In the third of present study, regional changes of calcium and energy metabolism were studied in the later stage of recirculation after 15 min forebrain ischemia. Although tissue ATP content recovered to normal at 6 hours after the recirculation, it gradually decreased in the hippocampal subiculum-CA1 regions as the recirculation time increased. In the regions of reduced ATP content, an alkaline pH shift and loss of Nissl's staining were noted. Abnormal calcium stains were seen in the cortical neurons in layers 3 and 5-6, the hippocampal Ammon's horn and the ventral postero-lateral thalamic nucleus. The distribution of these calcium stains was almost consistent with that in the second study. In the hippocampal subiculum-CA1 regions, the abnormal calcium stains preceded the alteration of ATP and tissue pH. Abnormality in the calcium staining was also noted in the hippocampal CA3-CA4 regions and the ventral postero-lateral thalamic nucleus, where the decrease of ATP or the histopathological change did not develop.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Alteration of regional calcium and energy metabolism in ischemic neuronal injury]. 280 14

Opioid ([3H]naloxone) and spirodecanone ([3H]spiperone) binding sites in the hippocampus were visualized in the Mongolian gerbil and in the rat using in vitro autoradiography. In the hippocampus, marked differences were noted in the stratum (sr.) pyramidale of the CA1 subfield where opioid and spirodecanone (assayed in the presence of mianserin and sulpiride) binding activities were very low in gerbils, but high in rats. Gerbils exhibited a high concentration of [3H]naloxone binding sites in the sr. pyramidale of the CA3 subfield, as observed in the rat. In addition, the gerbil has a very high opioid receptor density in the hilar region and in the sr. moleculare of the dentate gyrus. The cellular localization of opioid and spirodecanone receptor sites was studied in the rat hippocampus using selective neuronal damage to CA1 and CA3 neurons by means of ischemia and kainic acid treatment, respectively. The results suggest that the gerbil differs from the rat with respect to the characteristic pyramidal cells (spirodecanone binding site) and interneurons (opioid receptor) in the CA1 subfield of the hippocampus. Distinct localization of opioid and spirodecanone receptors in the gerbil provides a good model with which to investigate the electrophysiological and biochemical roles of opioid peptides and butyrophenone spirodecanone drugs.
 ...
PMID:Autoradiographic localization of opioid and spirodecanone receptors in the gerbil hippocampus as compared with the rat hippocampus. 283 28

In this chapter, the pathophysiology and neurochemical pathology of epileptic brain damage is discussed on the basis of an integrative approach in which a comparison is made to cell necrosis resulting from ischemia and hypoglycemia. Two main questions are asked. First, is the brain damage resulting from these three disorders of cerebral energy metabolism similar in distribution and structural characteristics, as previously proposed? Second, is it possible to identify one or several neurochemical events, at the cellular and subcellular level, that qualify as the final common pathways leading to neuronal necrosis? A related question is, will seizures cause structural damage even if they do not critically curtail cellular oxygen supply? A review of the literature and of recent results obtained in animals with long-term recovery following status epilepticus of known duration suggests that although brain damage caused by epilepsy shows some similarities to that incurred due to ischemic and hypoglycemic insults, it is far from identical. In well oxygenated animals with an adequate cardiovascular function, 2 hr of status epilepticus causes moderate neuronal necrosis in the cerebral cortex (layers 3-4), the hippocampus (CA4 and CA1 pyramidal cells), and the thalamus (ventromedial nuclei). In rats, status epilepticus of 30 min duration or longer invariably causes infarction of the substantia nigra (pars reticularis), with some affectation of globus pallidus as well. Notably, CA3 pyramids and dentate neurons are spared, as is the pars compacta of the substantia nigra. Neurochemical events in ischemia, hypoglycemia, and status epilepticus show some striking dissimilarities, yet all three conditions lead to neuronal necrosis. In complete or near-complete ischemia, in which metabolic rate virtually ceases; deterioration of tissue energy state is rapid and extensive, with dramatic loss of ion homeostasis; cellular redox systems are reduced; and acidosis is marked to excessive. In hypoglycemic coma, oxygen consumption continues, albeit at a reduced rate; loss of high energy phosphates is extensive but less than complete, as is loss of ion homeostasis; cellular redox system become oxidized; and acidosis is absent. In epileptic seizures, finally, metabolic rate is markedly enhanced; perturbation of tissue energy state and of ion homeostasis is minimal to small; and acidosis is moderate. Results obtained in experimental animals suggest that neuronal necrosis, when incurred, is unrelated to energy failure and occurs in spite of adequate cellular oxygenation. Four neurochemical events are common to all three conditions discussed.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Epileptic brain damage: pathophysiology and neurochemical pathology. 287 25

The contribution of excitatory inputs to CA1 pyramidal cell death after ischemia was examined using rats with unilateral destruction of CA3 pyramidal cells. Intracerebroventricular injection of L-alpha-kainic acid (KA) was performed before the induction of transient forebrain ischemia. Five days after ischemic insult, pyramidal cells and L-glutamate binding sites in the CA1 region ipsilateral to the KA injection were preserved in spite of neuronal necrosis and a significant decrease in L-glutamate receptor density in the contralateral CA1 region, indicating the critical role of Schaffer collaterals in delayed neuronal death.
 ...
PMID:Lesions to Schaffer collaterals prevent ischemic death of CA1 pyramidal cells. 287 20

We examined the effect of lidocaine on ischemic neuronal injury in the rat forebrain ischemia model. Cerebral ischemia was achieved with bilateral carotid artery occlusion and controlled hypotension to a mean of 50 torr for 10 minutes. Perfusion-fixation was performed 7 days after ischemia, subsequent to which the brains were sectioned coronally and stained with hematoxylin and eosin. Ischemic neuronal injury was quantitatively expressed (after direct counting) as a percentage of total neurons, that is, ischemic neurons divided by (ischemic neurons + normal neurons). Predictably, the selectively vulnerable hippocampal areas exhibited the most marked neuronal injury. In the CA1/CA2 sectors, lidocaine-treated rats demonstrated less injury (34 +/- 14%) than untreated (64 +/- 9%) or saline-treated (70 +/- 10%) rats. However, these superficially pronounced numerical differences were not of statistical significance (p greater than 0.05). In the CA3 sector, neuronal injury in lidocaine-treated rats (31 +/- 14%) was significantly different at p less than 0.05 from the untreated (80 +/- 5%) but not the saline-treated (59 +/- 13%) group. We conclude that lidocaine may have an only marginal beneficial effect on forebrain ischemia in rats.
 ...
PMID:Effect of lidocaine on forebrain ischemia in rats. 291 25


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