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

The effects of naftidrofuryl on postischemic neuronal damage and on local cerebral blood flow (LCBF) were examined in a rat model of forebrain ischemia (occlusion of carotid arteries and hypotension). Ischemia was induced for 10 min. LCBF was measured after 2 and 10 min of recirculation. A histological evaluation of cell loss in the hippocampal areas was performed 7 days after ischemia. Naftidrofuryl (10 mg/kg) was administered intraperitoneally 15 min before ischemia. The drug reduced the percentage of necrotic neurons in the CA1 and CA4 sector of the hippocampus, while the LCBF of these hippocampal sections was not significantly altered. Thus, naftidrofuryl is suggested to protect hippocampal neurons against ischemic damage mainly by a direct effect on brain parenchyma.
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PMID:Naftidrofuryl protects neurons against ischemic damage. 275 48

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)
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PMID:[Alteration of regional calcium and energy metabolism in ischemic neuronal injury]. 280 14

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)
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PMID:Epileptic brain damage: pathophysiology and neurochemical pathology. 287 25

Mitochondrial respiratory function, assessed from the rate of oxygen uptake by homogenates of rat brain subregions, was examined after 30 min of forebrain ischemia and at recirculation periods of up to 48 h. Ischemia-sensitive regions which develop extensive neuronal loss during the recirculation period (dorsal-lateral striatum, CA1 hippocampus) were compared with ischemia-resistant areas (paramedian neocortex, CA3 plus CA4 hippocampus). All areas showed reductions (to 53-69% of control) during ischemia for oxygen uptake rates determined in the presence of ADP or an uncoupling agent, which then recovered within 1 h of cerebral recirculation. In the ischemia-resistant regions, oxygen uptake rates remained similar to control values for at least 48 h of recirculation. After 3 h of recirculation, a significant decrease in respiratory activity (measured in the presence of ADP or uncoupling agent) was observed in the dorsal-lateral striatum which progressed to reductions of greater than 65% of the initial activity by 24 h. In the CA1 hippocampus, oxygen uptake rates were unchanged for 24 h, but were significantly reduced (by 30% in the presence of uncoupling agent) at 48 h. These alterations parallel the development of histological evidence of ischemic cell change determined previously and apparently precede the appearance of differential changes between sensitive and resistant regions in the content of high-energy phosphate compounds. These results suggest that alterations of mitochondrial activity are a relatively early change in the development of ischemic cell death and provide a sensitive biochemical marker for this process.
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PMID:Altered mitochondrial respiration in selectively vulnerable brain subregions following transient forebrain ischemia in the rat. 366 30

Regional cerebral protein synthesis was investigated in the Mongolian gerbil during recovery from forebrain ischemia produced by bilateral common carotid artery occlusion for 5 min. At various recirculation periods up to 72 h animals received a single dose of L-(3,5-3H)tyrosine and were killed 30 min later. Brains were processed for autoradiography using the stripping film technique. During the initial 30 min of recirculation autoradiographs revealed an almost complete inhibition of protein synthesis in all forebrain structures with the exception of the medio-dorsal thalamic nuclei. Between 30 min and 12 h of recirculation amino acid incorporation was completely restored in neurons of the cerebral cortex, basal ganglia, hippocampal CA3 and CA4 zones and the dentate gyrus. In CA1, early (90-min postischemia) and progressive recovery of a few irregularly dispersed neurons was observed, but the vast majority of pyramidal cells never regained their normal biosynthetic activity. Between 3 and 6 h of recirculation CA1 neurons showed faint labeling, followed by a secondary deterioration resulting in complete lack of incorporation within 12 h after restoration of blood flow. Autoradiographs at all subsequent time points exhibited persistent inhibition of protein synthesis in CA1 until neuronal necrosis occurred 2-3 days later. Thus, in contrast to ischemia-resistant cell populations with rapid progressive and complete restoration of protein synthesis, hippocampal neurons undergoing delayed necrosis are characterized by an early incomplete recovery immediately followed by a secondary persistent inhibition.
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PMID:Persistent inhibition of protein synthesis precedes delayed neuronal death in postischemic gerbil hippocampus. 377 78

The density and distribution of brain damage after 2-10 min of cerebral ischemia was studied in the rat. Ischemia was produced by a combination of carotid clamping and hypotension, followed by 1 week recovery. The brains were perfusion-fixed with formaldehyde, embedded in paraffin, subserially sectioned, and stained with acid fuchsin/cresyl violet. The number of necrotic neurons in the cerebral cortex, hippocampus, and caudate nucleus was assessed by direct visual counting. Somewhat unexpectedly, mild brain damage was observed in some animals already after 2 min, and more consistently after 4 min of ischemia. This damage affected CA4 and CA1 pyramids in the hippocampus, and neurons in the subiculum. Necrosis of neocortical cells began to appear after 4 min and CA3 hippocampal damage after 6 min of ischemia, while neurons in the caudoputamen were affected first after 8-10 min. Selective neuronal necrosis of the cerebral cortex worsened into infarction after higher doses of insult. Damage was worst over the superolateral convexity of the hemisphere, in the middle laminae of the cerebral cortex. The caudate nucleus showed geographically demarcated zones of selective neuronal necrosis, damage to neurons in the dorsolateral portion showing an all-or-none pattern. Other structures involved included the amygdaloid, the thalamic reticular nucleus, the septal nuclei, the pars reticularis of the substantia nigra, and the cerebellar vermis.
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PMID:The density and distribution of ischemic brain injury in the rat following 2-10 min of forebrain ischemia. 650 48

Following brief ischemia, the Mongolian gerbil is reported to develop unusual hippocampal cell injury (Brain Res 239:57--69, 1982). To further clarify this hippocampal vulnerability, gerbils were subjected to ischemia for 3, 5, 10, 20, and 30 min by bilateral occlusion of the common carotid arteries. They were perfusion-fixed after varying intervals of survival time ranging from 3 h up to 7 days. Following brief ischemia (5--10 min), about 90% of the animals developed typical hippocampal damage. The lesion was present throughout the extent of the dorsal hippocampus, whereas damage outside the hippocampus was not observed. Each sector of the hippocampus showed different types of cell reaction to ischemia. Ischemia cell change was seen in scattered CA4 neurons , and reactive change was found in CA2, whereas CA1 pyramidal cells developed a strikingly slow cell death process. Ischemia for 3 min did not produce hippocampal lesion in most cases. Following prolonged ischemia (20--30 min), brain injury had a wide variety in its extent and distribution. These results revealed that the gerbil brief ischemia model can serve as an excellent, reliable model to study the long-known hippocampal selective vulnerability to ischemia. Delayed neuronal death in CA1 pyramidal cells was confirmed after varying degrees of ischemic insult. These findings demonstrated that the pathology of neuronal injury following brief ischemia was by no means uniform nor simple.
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PMID:Selective vulnerability in the gerbil hippocampus following transient ischemia. 669 54

In the CA1 subfield of the gerbil hippocampus, an unusual series of changes were noticed after ischemia. Mongolian gerbils were subjected to bilateral carotid occlusion for 5 min. Perfusion fixation was performed 3, 6 and 12 h or 1, 2, 4, 7 and 21 days afterwards. Specimens obtained from the dorsal hippocampus were processed for light and electron microscopy. Three different types of changes were observed in the CA4, CA2 and CA1 subfields. In CA4, the change was rapid and corresponded to ischemic cell change. The alteration in CA2 was relatively slow, and identical to what has been called reactive change. On the contrary, the change in the CA1 pyramidal cells was very slow, only becoming apparent by light microscopy 2 days following ischemia. The CA1 subfield was selected for electron microscopic observation. The lamellar alignment of proliferated cisterns of the endoplasmic reticulum was the most conspicuous finding in these cells. Four days following ischemia, almost all of the pyramidal cells in CA1 were destroyed. In the CA1 neuropil, numerous presynaptic terminals remained without being apposed to normal postsynaptic sites. These changes in CA1, called here 'delayed neuronal death', may differ from those thought to be typical of ischemic neuronal damage. It was unlikely that the disturbance of local blood vessels was the cause of these changes.
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PMID:Delayed neuronal death in the gerbil hippocampus following ischemia. 709 91

Tyrosine phosphorylation in the gerbil hippocampus after a transient ischemia was analyzed by immunoblotting and immunohistochemistry. In control hippocampus, the phosphotyrosine was detected in many proteins of 165 to 10 kDa and the immunostain showed a distinct distribution. The ischemic insult induced various alterations of the phosphotyrosine immunoreactivities in both ischemia-resistant and -vulnerable neurons which were associated with alterations in the expression of 165 to 19 kDa-immunoreactive bands. These results suggest that tyrosine phosphorylation is involved in the ischemic hippocampus to play a role in the development of early and delayed neuronal deaths in CA4 and CA1 neurons, respectively.
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PMID:Stimulation of protein-tyrosine phosphorylation in gerbil hippocampus after global forebrain ischemia. 751 68

We investigated the changes of copper/zinc superoxide dismutase (CuZn-SOD) and manganese superoxide dismutase (Mn-SOD) in the rat hippocampus after 10 min of cerebral ischemia induced by 4-vessel occlusion. The rats were allowed to survive for 4 h, 1 day, 3 days, and 7 days after ischemia. The distribution of SODs were determined by immunohistochemical staining with antibodies against rat CuZn-SOD and Mn-SOD. CA1 pyramidal neurons and granule cells of the dentate gyrus showed intense CuZn-SOD immunoreactivity, whereas CA3 and CA4 neurons showed weaker immunostaining than CA1 neurons in normal animals. The immunoreactivity was reduced by 4 h after ischemia in CA1, CA3, and CA4 neurons when no histological damage was observed. Mn-SOD immunostaining revealed more intense immunoreactivity in CA3 pyramidal neurons than in CA1 neurons in normal animals. Interneurons in the CA1 and CA3 regions and the dentate hilus also showed high Mn-SOD immunostaining. Although CA1 neurons lost Mn-SOD immunoreactivity by 1 day after ischemia, CA3 neurons and interneurons retained the immunoreactivity and preserved intact cell contour after ischemia. In addition, reactive glial cells, which were differentiated by immunocytochemical staining against glial fibrillary acidic protein for reactive astrocytes and histochemical staining for reactive microglial cells, were intensely stained for CuZn-SOD and Mn-SOD after ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An immunohistochemical study of copper/zinc superoxide dismutase and manganese superoxide dismutase in rat hippocampus after transient cerebral ischemia. 769 76


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