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

We investigated the pathogenic role of free radical formation in ischemic neuronal death using radical scavenger, superoxide dismutase. Cerebral ischemia was produced in the gerbil by bilateral common carotid occlusion for 5 min, which consistently resulted in delayed neuronal death in the CA1 region of the hippocampus. The effects of free superoxide dismutase and a derivatized superoxide dismutase, pyran copolymer conjugated superoxide dismutase, on early ischemic damages, detected sensitively by the immunohistochemical reaction for microtubule associated protein 2, and a subsequent delayed neuronal death after restoration of blood flow were investigated. Preischemic treatment by pyran conjugated superoxide dismutase showed clear protective effects against both the neuronal damages detected by immunohistochemistry after 5 min ischemia and the delayed neuronal necrosis after one week of recovery, although no clear beneficial effects were observed when this drug was administered just before the recirculation or free superoxide dismutase was used. These results strongly suggest that free radical generation during brief period of ischemia plays a pivotal role in triggering the ischemic neuronal damages causing delayed neuronal death at the selectively vulnerable areas of the brain.
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PMID:Free radical generation during brief period of cerebral ischemia may trigger delayed neuronal death. 219 42

Neonatal rats were subjected to transient cerebral hypoxic-ischemia (unilateral occlusion of the common carotid artery + 7.70% O2 for 100 min) and allowed to recover for 3 h, 24 h, 2 days or 14 days. Consecutive tissue sections were stained with antibodies against alpha-fodrin, the 150 kDa breakdown product of alpha-fodrin (FBDP, marker of calpain proteolysis) or microtubule associated protein 2 (MAP 2, marker of dendrosomatic neuronal injury). Cortical tissue pieces were subjected to Western blotting using the antibody against the FBDP. Areas with brain injury displayed a distinct loss of MAP 2 which clearly delineated the infarct. FBDP accumulated in injured and borderline regions ipsilaterally and a less conspicuous, transient increase in FBDP also occurred in the contralateral hemisphere, especially in the white matter. A reciprocal staining pattern could be seen in the cerebral cortex, i.e. loss of MAP 2 and accumulation of FBDP, most pronounced 14 days after the insult. Fodrin and MAP 2 are known calpain substrates, and degradation of these proteins preceded neuronal degeneration, indicating that these proteases may be involved in the early events triggering the cascades leading to neuronal death.
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PMID:Degradation of fodrin and MAP 2 after neonatal cerebral hypoxic-ischemia. 758 14

Changes of immunoreactivities for microtubule based motor proteins, kinesin and cytoplasmic dynein, and non-motor protein, microtubule associated protein (MAP) 2 were investigated in gerbil hippocampus after transient ischemia. The immunoreactivities for kinesin showed a progressive decrease in hippocampal CA1 cells from 8 h after transient 5 or 15 min of ischemia that is lethal to the CA1 cells, while it showed no change after 2 min of ischemia that is non-lethal to the cells. The immunoreactivities for cytoplasmic dynein showed a decrease from 3 or 1 h of reperfusion in the CA1 cells after 5 or 15 min of ischemia, respectively. In contrast, the immunoreactivity for MAP2 remained normal until 2 days in the CA1 cells after 5 min of ischemia. These results showed an early changes of microtubule based motor proteins, such as kinesin and cytoplasmic dynein in vulnerable CA1 neurons. These changes may affect the mitochondrial shuttle system between neuronal cell body and the peripheries such as axon terminal and dendrites. This early disturbance may cause a failure to obtain newly synthesized nuclear encoded mitochondrial protein, and result in mitochondrial dysfunctions and the subsequent cell death.
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PMID:Early immunohistochemical changes of microtubule based motor proteins in gerbil hippocampus after transient ischemia. 771 74

The inflammatory response following hypoxic-ischemia (HI) in the neonate is largely unknown. Presently, the expression of microglial antigens and the beta-amyloid precursor protein (APP) were studied in relation to a dendrosomatic marker of neuronal injury (microtubule associated protein II; MAP II). HI was induced in 7-day-old rats by the combined unilateral carotid ligation and hypoxia. The pups (n = 23) were perfusion fixed 2-3 h, 24 h, 2-4 days and 14 days after HI and compared to sham-operated controls (n = 6). Antibodies were used for detection of the major histocompatibility complex II (OX-6), major histocompatibility complex I (OX-18) and complement receptor type 3 (OX-42), APP (APP 676-695) and MAP II (monoclonal MAP II) antigens. There was a transient APP expression 2-3 h after HI. A slight increase of microglial antigens (OX-18) was seen in the white matter 2 h after HI followed by a marked increase of OX-18, OX-6, OX-42 antigens 24 h-3-4 days in most injured regions with exception of the thalamus where a delayed (14 days) microglial response was seen. The latter event was parallelled by a delayed loss of MAP II. In conclusion, intense microglial expression occurs after neonatal HI either with an acute or delayed time-course depending on brain region.
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PMID:Microglia activation after neonatal hypoxic-ischemia. 774 44

Alteration of evolution of delayed neuronal death in the gerbil after intraperitoneal injection of nicardipine was investigated by using immunohistochemistry for microtubule associated protein (MAP) which enables early detection of ischemic injuries. Male Mongolian gerbils were subjected to intraperitoneal injection of nicardipine at concentrations of 0.01-10 mg/kg and subsequent occlusion of bilateral carotid arteries for 5 min. Extent of the lesions estimated by immunohistochemistry for MAP was reduced at the dosages of 0.2 mg/kg nicardipine as compared with control, while lesser or larger amounts have failed to protect the brain tissue from ischemic insults. Furthermore, pre- and postoperative treatment of 0.2 mg/kg of nicardipine two times daily succeeded to partially attenuate the development of delayed neuronal death in gerbils which underwent ischemia for 5 min and subsequent reperfusion for 4 days. These results indicate that optimal concentration of nicardipine ameliorates delayed neuronal death, presumably because of the increase of cerebral blood flow and intervention of intracellular influx of calcium ions.
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PMID:[Protective effect of nicardipine hydrochloride on the evolution of delayed neuronal death--an immunohistochemical study]. 819 40

Microglial and astrocyte responses to glucocorticoid pretreatment in the neonate exposed to hypoxia-ischemia (HI) are largely unknown. The expression of microglial antigens and astrocytic proliferation was compared in neonatal rats exposed to HI with and without cortisone. HI was induced in 7 day old rats. One group of rats received cortisone within 24 h of birth. Immunocytochemical and immunoblot investigations were performed. Monoclonal antibodies (OX18 and OX42) were used for the detection of the major histocompatibility complex (MHC) class I antigens and complement receptor 3 (CR3) respectively. Antibodies directed against glial fibrillary acidic protein (GFAP) and microtubule associated protein II (MAP II) were used to evaluate the extent of brain damage. Cortisone treatment provoked a decline in the number of microglial cells but did not modify GFAP levels in control rats which were not exposed to HI. Neuronal damage was similar in control and cortisone treated rats exposed to HI. There were also similarities in the expression of CR3 antigens on microglia. However microglial cells expressing MHC class I antigens were less prevalent in rats exposed to HI only. Cortisone pretreatment enhanced the expression of MHC class I antigens. Astrocytic proliferation was intense in rats exposed to HI; however in rats treated with cortisone and exposed to HI there was a drastic reduction in astrocytic proliferation. In conclusion it is suggested that microglia which survive cortisone pretreatment become over-activated thereby preventing astrocytic proliferation.
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PMID:Microglia-astrocyte interactions after cortisone treatment in a neonatal hypoxia-ischemia model. 881 76

Although adenosine receptor-based treatment of cerebral ischemia and other neurodegenerative disorders has been frequently advocated, cardiovascular side effects and an uncertain therapeutic time window of such treatment have constituted major obstacles to clinical implementation. Therefore, we have investigated the neuroprotective effects of the adenosine A1 receptor agonist adenosine amine congener (ADAC) injected after either 5 or 10 min ischemia at 100 micrograms/kg. When the drug was administered at either 6 or 12 h following 5 min forebrain ischemia, all animals were still alive on the 14th day after the occlusion. In both ADAC treated groups neuronal survival was approximately 85% vs. 50% in controls. Administration of a single dose of ADAC at times 15 min to 12 h after 10 min ischemia resulted in a significant improvement of survival in animals injected either at 15 or 30 min, or at 1, 2, or 3 h after the insult. In all 10 min ischemia groups, administration of ADAC resulted in a significant protection of neuronal morphology and preservation of microtubule associated protein 2 (MAP-2). However, postischemic Morris' water maze tests revealed full preservation of spatial memory and learning ability in animals injected at 6 h. On the other hand, the performance of gerbils treated at 12 h postischemia was indistinguishable from that of the controls. Administration of ADAC at 100 micrograms/kg in non-ischemic animals did not result in bradycardia, hypotension, or hypothermia. The data indicate that when ADAC is used postischemically, the most optimal level of protection is obtained when drugs are given at 30 min to 6 h after the insult. Although the mechanisms involved in neuroprotective effects of adenosine A1 receptor agonists require further studies, the present results demonstrate the feasibility of their clinical applications.
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PMID:Postischemic administration of adenosine amine congener (ADAC): analysis of recovery in gerbils. 898 84

The goal of the present study was to determine the neuroprotective efficacy of ischemic preconditioning using behavioral, electrophysiological and histological endpoints at various time points up to 90 days postischemia. Gerbils were exposed to a brief, non-injurious episode of forebrain ischemia (1.5 min) on each of 2 consecutive days. Three days following this preconditioning procedure, the animals received a 5 min occlusion. Other animals underwent sham surgery or a 5 min occlusion without preconditioning. Ischemic preconditioning appeared to provide striking histological protection at both rostral (approximately 80% and approximately 67% of sham) and posterior levels of hippocampus (approximately 94% and approximately 78% of sham) at 3 and 10 days survival, respectively. However, in spite of the near normal number of CA1 neurons, animals displayed marked impairments in an open field test of habituation as well as reduced dendritic field potentials in the CA1 area. Additionally, in ischemic animals the basal and apical dendritic regions of CA1 were nearly devoid of the cytoskeletal protein microtubule associated protein 2 (MAP2). Staining levels of MAP2 in preconditioned and sham animals were similar. With increasing survival time, open field behavior as well as CA1 field potential amplitude recovered. Nonetheless, CA1 cell death in ischemic preconditioned animals continued over the 90-day survival period (P<0.05, vs. sham levels). Ischemic preconditioning provides a significant degree of neuroprotection characterized by a complex interplay of protracted cell death and neuroplasticity (recovery of function). These competing processes are best elucidated using a combination of functional and histological endpoints as well as multiple and extended survival times (i.e., greater than 7-10 days).
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PMID:Competing processes of cell death and recovery of function following ischemic preconditioning. 963 May 61

The effects of brain-derived peptides (BDP; Cerebrolysin) upon the amount of brain injury due to focal brain ischemia were assessed. Male Thomae rats were divided randomly into a sham-operated group (n = 5), an ischemic control (untreated) group (n = 7) and an ischemic BDP-treated group (n = 6) and subjected to reversible middle cerebral artery occlusion (MCAO) for 2h followed by 90min of reperfusion. Local cortical blood flow (LCBF) was monitored by Laser-Doppler flowmetry to assess the MCAO and to measure the blood flow in regions peripheral to the infarction. Infarcted areas of the hippocampus and subcortical structures were quantified in hematoxylin and eosin (H&E) stainings. Functional disturbances of the neurons were detected by immunohistochemical staining of the microtubule associated protein MAP2. Moreover, brain edema was estimated morphometrically. LCBF was estimated from the periphery of infarcted areas and was reduced to 55 to 65% of baseline values (p < 0.05). Reperfusion led to LCBF being increased again to baseline values. No differences in LCBF between the control and the BDP-treated animals were found. In the hippocampus, BDP-treated animals showed a significant reduction of loss of MAP2 immunoreactivity in the subiculum and CA1 region by 59% and 64%, respectively, in comparison to control animals (p < 0.05). The amount of irreversibly damaged neurons in these regions was decreased in tendency. However, the inner blade of the dentate gyrus in BDP-treated animals showed a significant reduction of neuronal injury by 98% (p < 0.05). Likewise, BDP treatment reduced the size of the areas showing a loss of MAP2 immunoreactivity in the thalamic and hypothalamic structures by 51% and in the mesencephalon by 81% (p < 0.05). The size of the infarcted areas in these regions (H&E) was reduced in tendency. In the caudate putamen, no protective effect of BDP-treatment could be proven. Cerebral infarction was accompanied by an increase in the volume of the ischemic hemisphere by 10 +/- 1% in the control and 8 +/- 1% in the BDP-treated animals. These findings indicate a beneficial effect for BDP treatment in ameliorating the early effects of focal brain ischemia.
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PMID:Brain-derived peptides reduce the size of cerebral infarction and loss of MAP2 immunoreactivity after focal ischemia in rats. 970 Jun 66

We have previously shown that chronic administration of the selective A3 receptor agonist N6-(3-iodobenzyl)-5'-N-methylcarboxoamidoadenosine (IB-MECA) leads to a significant improvement of postocclusive cerebral blood flow, and protects against neuronal damage and mortality induced by severe forebrain ischemia in gerbils. Using immunocytochemical methods we now show that chronic with IB-MECA results in a significant preservation of ischemia-sensitive microtubule associated protein 2 (MAP-2), enhancement of the expression of glial fibrillary acidic protein (GFAP), and a very intense depression of nitric oxide synthase in the brain of postischemic gerbils. These changes demonstrate that the cerebroprotective actions of chronically administered IB-MECA involve both neurons and glial cells, and indicate the possibility of distinct mechanisms that are affected in the course of chronic administration of the drug.
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PMID:Chronic administration of adenosine A3 receptor agonist and cerebral ischemia: neuronal and glial effects. 1007 88


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