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

Expression of sulfated glycoprotein-2 (SGP-2) mRNA was studied by in situ hybridization in rat brains submitted to transient forebrain ischemia of 30 min. Induction of this multifunctional protein has been previously observed following diverse types of brain lesions, and an involvement in programmed cell death and synaptic remodelling has been proposed. Ischemia was produced by four-vessel occlusion and followed by various recirculation times ranging from 15 min to 7 days. Up to 6 h after ischemia SGP-2 mRNA did not change in any brain region. After 12 h recirculation, SGP-2 mRNA induction was observed in the stratum lacunosum moleculare of CA1 sector of hippocampus. This induction peaked at 3 days recirculation and then declined. From 24 h recirculation onward, induction also occurred in patchy areas of the cortex, and after 7 days recirculation in the ventral thalamus and in a corona around lesioned parts of the striatum. No induction occurred at any recirculation time in pyramidal neurons of hippocampus or other neuronal populations that are damaged by ischemia. The combination of in situ hybridization with GFAP immunohistochemistry revealed that SGP-2 mRNA was mainly induced in reactive actrocytes. This excludes a direct involvement in ischemic neuronal death and supports the possible participation in the post-lesional reorganization of the tissue.
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PMID:Sulfated glycoprotein-2 mRNA in the rat brain following transient forebrain ischemia. 811 19

Recently, we demonstrated that transient forebrain ischemia in rats leads to an early and strong induction of basic fibroblast growth factor (bFGF) synthesis in astrocytes in the injured brain regions. In this study, in order to clarify the targets of such raised endogenous bFGF levels, the messenger RNA (mRNA) expression of its receptors (flg and bek) in the hippocampus following transient forebrain ischemia induced by four-vessel occlusion for 20 min was investigated using an in situ hybridization technique. Transient forebrain ischemia induced an increase in the number of flg mRNA-positive cells from an early stage (24 h after ischemia) in the hippocampal CA1 subfield where delayed neuronal death occurred later (48-72 h after ischemia). This increase became more marked with the progression of neuronal death and was still evident in the same area 30 days later. The time course of the appearance and distribution pattern of flg mRNA-positive cells in the CA1 subfield were quite similar to those of bFGF mRNA-positive cells. On the other hand, in situ hybridization for bek mRNA showed only slight and transient (observed 72 h and 5 days after ischemia) increases in the number of mRNA-positive cells in the CA1 subfield following ischemia. The use of in situ hybridization and glial fibrillary acidic protein immunohistochemistry in combination demonstrated that the cells in the CA1 subfield that exhibited ischemia-induced flg or bek mRNA expression were astrocytes. These data indicate that transient forebrain ischemia induces upregulation of fibroblast growth factor-receptor expression, accompanied by increased bFGF expression in astrocytes, and suggest that the increased astrocytic bFGF levels in injured brain regions act on the astrocytes via autocrine systems and are involved in the development and maintenance of astrocytosis.
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PMID:Upregulation of fibroblast growth factor-receptor messenger RNA expression in rat brain following transient forebrain ischemia. 815 41

Middle aged rats (13 months) were subjected to chronic cerebrovascular insufficiency (CVI) for 9 weeks using a 3-vessel occlusion technique. This CVI injury targets CA1 neuron damage selectively. Three groups of rats had their cerebral blood flow restored after 1, 2 or 3 weeks following CVI by removal of their carotid artery occluders. Another rat group did not undergo deocclusion for the 9 week observation period. Rats were tested for memory acquisition and retention 6 and 9 weeks after CVI using a modified water maze test. At the end of the 9 weeks, cerebral blood flow was measured in the fronto-parietal cortex and rats were killed by fixation-perfusion. Hippocampal morphometry was done to assess the % of damaged CA1 neurons and the density of GFAP-positive hyperplasia and hypertrophy. Results show that restoration of cerebral blood flow 1 and 2 weeks after CVI but not after 3 weeks of CVI, reversed a significant increase in reactive astrocytosis and prevented memory impairment in these deoccluded rats when compared to the non-deoccluded group. It appears from these results that 'neuronal rescue' of CA1 neurons is possible when cerebral blood flow is restored in rats subjected to chronic CVI during a 2 week (but not 3 week) 'window of opportunity'. This chronic brain ischemia model may be useful in screening potential therapy in patients with dementia where spatial memory impairment and hippocampal damage may be manifested.
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PMID:Brain blood flow restoration 'rescues' chronically damaged rat CA1 neurons. 822 Oct 94

Although specific patterns of cellular vulnerability have been identified in experimental models of cerebral ischemia, there is little data on the occurrence of similar abnormalities in human ischemia. We therefore used a variety of histochemical methods to define changes affecting specific classes of cells in post-mortem specimens from seven patients with hippocampal and neocortical ischemic lesions. In acute lesions, staining with SMI-32, an antibody directed against nonphosphorylated neurofilaments that labels pyramidal projection neurons, was prominently depleted even when conventional Nissl staining revealed only mild pyknosis. In contrast, staining for other markers such as microtubule-associated protein 2 (MAP-2), another cytoskeletal protein, or parvalbumin, a calcium-binding protein found in gamma-aminobutyric acid (GABA)-ergic interneurons, were relatively preserved. SMI-32 antibody also labeled dystrophic axons and axonal retraction balls in and around acute ischemic lesions. The pattern of differential changes in immunoreactivity was essentially the same in all acute ischemic injuries, including both diffuse lesions in the CA1 field (Sommer's sector) and discrete infarcts in CA1 and neocortex. In addition, immunoreactivity for the immediate early gene product c-fos was enhanced in and around the acute ischemic lesions that we studied. In some very acute lesions, immunoreactivity for glial fibrillary acidic protein (GFAP) was depleted in areas of severe ischemia and necrosis, but, as expected, GFAP immunoreactivity was increased in lesions more than a few days old. In contrast, the loss of SMI-32 immunoreactivity persisted in chronic lesions. These findings are consistent with those of experimental ischemia in animals and confirm the relevance of these studies for human cerebral ischemia. The pattern of selective changes also resembles that of injuries induced directly by excitatory amino acids, which may play a significant role in the pathogenesis of ischemic damage.
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PMID:Immunohistochemical patterns of selective cellular vulnerability in human cerebral ischemia. 827 38

It is not entirely clear whether the proliferative changes in astrocytes following cerebral ischemia are in response to neuronal injury or are secondary to the direct effects of ischemia on the astrocytes. Therefore, the following study examined the relationship between post-ischemic astrocytosis with the extent of neuronal necrosis and the severity of the ischemia. Astrocyte reactivity was assessed by alterations in glial fibrillary acidic protein (GFAP), using immunohistochemistry and evaluation by optical density analysis. Cerebral ischemia was produced in rats by temporary occlusion of the carotid and vertebral arteris for 2, 10 and 30 min. This results in damage to the CA1 neurons after a characteristic delay of several days, the duration of which is inversely proportional to the severity of the ischemia. CA3 neurons are resistant to the ischemia and do not suffer permanent injury. The results showed that GFAP immunoreactivity significantly increased in the CA1 region after all three ischemic intervals but the rise of GFAP in the CA3 area reached significance only after 30 min of ischemia. The peak and duration of the GFAP increases thus correlated with the extent and the maturation of the neuronal necrosis. This suggests that with mild injury (2 and 10 min ischemia), post-ischemic astrocytosis is closely related to its neuronal environment rather than to the ischemic insult itself. Furthermore, the results showed an initial decrease in and delay of the subsequent GFAP rise.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between ischemia and ischemic neuronal necrosis to astrocyte expression of glial fibrillary acidic protein. 832 4

The effects of treatment with indole-pyruvic acid, an endogenous metabolite of tryptophan converted into kynurenic acid in the brain, were studied in rats after transient forebrain ischemia induced by the 4-vessel occlusion procedure. The histological analysis showed a significant protective effect of indole-pyruvic acid treatment on striatal ischemic lesions assessed by the extent of regional atrophy and the area of neuronal disappearance 14 days after ischemia. Striatal neurons were labelled by dopamine and adenosine 3':5' monophosphate regulated phosphoprotein-32 immunoreactivity. Conversely, increased neuronal loss, regional atrophy and glial fibrillary acidic protein immunoreactivity, an index of post-injury astroglial activation, were observed in the hippocampal formation, especially the CA3 field, of indole-pyruvic acid-treated rats when compared with vehicle-treated ischemic rats. The treatment with indole-pyruvic acid did not produce any improving effects in a test assessing short-term impairments after transient ischemia (motor test score at 24 h and 48 h post-ischemia). Furthermore, no significant effects of indole-pyruvic acid treatment were found on performance in water T-maze studied at 7 and 14 days post-ischemia. The opposite effects of indole-pyruvic acid on ischemic lesion in different brain regions may be related to its multiple neurochemical actions in the brain. The protective effect of indole-pyruvic acid on ischemic damage in striatum may be due to its conversion into kynurenic acid, a broad spectrum glutamate receptor antagonist. At hippocampal level, where glutamate receptor antagonists have been proved ineffective in the present lesion model, indole-pyruvic acid-induced changes in monamine availability may lead to a worsening of neuronal damage.
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PMID:Indole-pyruvic acid treatment reduces damage in striatum but not in hippocampus after transient forebrain ischemia in the rat. 836 38

Selective, delayed-onset vulnerability of hippocampal CA1 pyramidal cells has been reported as a unique phenomenon in man and the rat four-vessel occlusion (4-VO) model of global ischemia. This has become of great interest for clarification of CA1 pathophysiology and pharmacological intervention after global ischemia. Studies of pathophysiology and pharmacotherapy appear to be impeded by variability in specific criteria and duration of 4-VO ischemia for producing selective CA1 and differential CA1-CA3 damage. The goals of this study were to: (1) develop specific criteria for 4-VO ischemia to ensure selective, bilaterally symmetrical CA1 pyramidal cell damage, (2) examine the effects of 15 min of ischemia on concomitant CA1 cell necrosis and presence of remaining and/or "viable" neurons postischemia, (3) compare 15 and 30 min of ischemia on differential vulnerability of CA1-CA3 subfields, and (4) evaluate the effects of 15 min of ischemia on CA1 pyramidal cell necrosis and glial fibrillary acidic protein (GFAP)-positive astrocyte reactivity in CA1. After 15 min of ischemia, hippocampal pyramidal cell damage was well delineated, with CA1 severely damaged, but leaving CA3 virtually intact. In contrast, 30 min of ischemia produced severe CA1 and less severe CA3 necrosis. Histological evaluations across Days 1, 3, 6, and 14 indicated a significant delayed onset of CA1-CA3 cell necrosis by Day 3. Counting of remaining cells indicated a detectable loss of some large pyramidal neurons even 1 day after ischemia. Compared to controls, there was a differential increase in GFAP-positive astrocytes in CA1-CA3 after ischemia. The results provided quantitative data on the effects of specific 4-VO criteria and durations on: (1) selective CA1 cell necrosis, (2) differential CA1-CA3 cell vulnerability, (3) presence of postischemic remaining and/or viable neurons, and (4) prospect of a "therapeutic window" for pharmacological treatment of CA1 neuronal injury.
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PMID:Selective vulnerability and early progression of hippocampal CA1 pyramidal cell degeneration and GFAP-positive astrocyte reactivity in the rat four-vessel occlusion model of transient global ischemia. 843 46

Focal brain ischemia induced in rats by occlusion of an intracranial artery is a widely used paradigm of human brain infarct. Details of the structural changes that develop in either the human or the rat brain at various times after occlusion of an intracranial artery are incompletely characterized. We studied, in 48 adult Wistar rats, structural alterations involving the cerebral hemisphere ipsilateral to an arterial occlusion, at intervals ranging from 30 min to 7 days. Microscopic changes developed over time in separate areas of the corresponding cerebral hemisphere in a predictable pattern, appearing as small lesions in the preoptic area (30 minutes), enlarging to involve the striatum, and finally involving the cerebral cortex. Two types of neuronal responses were noted according to the time elapsed; acute changes (up to 6 hours) included scalloping, shrinkage, and swelling, whereas delayed changes (eosinophilia and karyolysis) appeared later (> or = 12 hours). Three types of astrocytic responses were noted. 1) Cytoplasmic disintegration occurred in the preoptic area at a time and in a place where neurons appeared minimally injured. 2) Nuclear and cytoplasmic swelling were prominent responses in the caudoputamen and cerebral cortex at a time when neurons showed minimal alterations. 3) Increased astrocytic glial fibrillary acidic protein reactivity was noted at the interface between the lesion and the surrounding brain tissue after 4 to 6 hours. The gross pattern of the brain lesion and the maturation of neuronal changes typical of a brain infarct have a predictable progression. Focal brain ischemia of up to 6-hour duration does not induce coagulation necrosis.
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PMID:Progression from ischemic injury to infarct following middle cerebral artery occlusion in the rat. 843 52

Glucose transport into nonneuronal brain cells uses differently glycosylated forms of the glucose transport protein, GLUT1. Microvascular GLUT1 is readily seen on immunocytochemistry, although its parenchymal localization has been difficult. Following ischemia, GLUT1 mRNA increases, but whether GLUT1 protein also changes is uncertain. Therefore, we examined the immunocytochemical distribution of GLUT1 in normal rat brain and after transient global forebrain ischemia. A novel immunocytochemical finding was peptide-inhibitable GLUT1 immunoreactive staining in parenchyma as well as in cerebral microvessels. In nonischemic rats, parenchymal GLUT1 staining co-localizes with glial fibrillary acidic protein (GFAP) in perivascular foot processes of astrocytes. By 24 h after ischemia, both microvascular and nonmicrovascular GLUT1 immunoreactivity increased widely, persisting at 4 days postischemia. Vascularity within sections of brain similarly increased after ischemia. Increased parenchymal GLUT1 expression was paralleled by staining for GFAP, suggesting that nonvascular GLUT1 overexpression may occur in reactive astrocytes. A final observation was a rapid expression of inducible heat shock protein (HSP)70 in hippocampus and cortex by 24 h after ischemia. We conclude that GLUT1 is normally immunocytochemically detectable in cerebral microvessels and parenchyma and that parenchymal expression occurs in some astroglia. After global cerebral ischemia, GLUT1 overexpression occurs rapidly and widely in microvessels and parenchyma; its overexpression may be related to an immediate early-gene form of response to cellular stress.
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PMID:Forebrain ischemia increases GLUT1 protein in brain microvessels and parenchyma. 853 May 57

This study investigated astroglial responses after focal cerebral ischemia in the rat cortex induced by photothrombosis. Astrocyte activation was studied at various time points by immunocytochemistry for glial fibrillary acidic protein (GFAP) and vimentin (VIM). We found a dual astrocytic response to focal ischemia: In the border zone of the infarct, GFAP-positive astrocytes were present within 2 days and persisted for 10 weeks. These astrocytes additionally expressed VIM. Remote from the ischemic lesion, cortical astrocytes of the entire ipsilateral hemisphere transiently expressed GFAP, but not VIM, beginning on day 3 after photothrombosis. This response had disappeared on day 14. By recording DC potentials, five to seven spreading depressions (SD) could be detected on the cortical surface during the first 2 h after photothrombosis. Treatment with MK801, a non-competitive NMDA-receptor antagonist, completely abolished SD and remote ipsilateral astrocytic activation, while the reaction in the border zone of the infarct remained unchanged. Functionally, persistent astrocytosis around the infarct might be induced by leukocyte-derived cytokines, while NMDA-receptor-mediated SD might cause remote responses.
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PMID:Astroglial responses in photochemically induced focal ischemia of the rat cortex. 854 65


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