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

Carotid arteries were occluded bilaterally for 15 min in two groups of Mongolian gerbils. The first group received 100% oxygen during the first 3 h of reperfusion. During that period, room air was given to the second group. After 3 h, both groups received room air. Brains of gerbils that died within 14 days after occlusion were removed, fixed in formalin and embedded in paraffin. Gerbils that survived 15-28 days were perfused with formalin before their brains were removed and embedded in paraffin. Adjacent, serially cut sections were stained with luxol fast blue (LFB)-H&E, cresyl violet, according to the Bodian method, or immunocytochemically with antisera raised against myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP). In brain sections of gerbils receiving 3 h of 100% oxygen, there were circumscribed white matter lesions in the corpus striatum, lateral thalamus, mesencephalon and posterior limb of the internal capsule. Myelin sheaths were swollen, fragmented and were less intensely stained by MBP antiserum. MBP and LFB-stained myelin fragments were present extracellularly and in macrophages. Many axons in these areas appeared undamaged. Previously described ischemic changes were found in gray matter and some areas of white matter in both groups. However, neurons in the deeper laminae of the cerebral cortex appeared to be better preserved in gerbils given oxygen. The results suggest that hyperoxia, if present immediately after transient brain ischemia, may damage myelin more severely than other cellular elements.
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PMID:Prominent white matter lesions develop in Mongolian gerbils treated with 100% normobaric oxygen after global brain ischemia. 232 46

Three aspects of the pathophysiology of experimental autoimmune encephalomyelitis (EAE) are discussed: firstly, the possible electrophysiological effects in the CNS of myelin basic protein, which is released during demyelination; secondly, the partial degeneration of monoaminergic and glutamatergic neurons which occurs during an attack of EAE in addition to demyelination; thirdly, the importance of ischemic events, accompanied by free radical release, in EAE. Especially the third aspect could have therapeutic implications. Treatment with radical scavengers, N-methyl-D-aspartate receptor blockers, or calcium blockers (as suggested for ischemia) might prove effective for EAE. Our present aim is to investigate whether these results are also relevant for MS, for which EAE is an animal model.
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PMID:Some pathophysiological aspects of experimental autoimmune encephalomyelitis. 247 88

The objective of this review is to provide an overview of the use of biochemical markers for the detection of Central Nervous System (CNS) complications after cardiac surgery and extracorporeal circulation (ECC). A computerized literature search in MEDLINE from 1966 onward was the basis for the references. The literature covering the following biochemical markers is reviewed: adenylkinase, creatine phosphokinase isoenzyme BB (CK-BB), lactate, neuron-specific enolase (NSE), S-100 protein, myelin basic protein, lactate dehydrogenase, aspartate aminotransferase, glutathione, vasointestinal neuropeptide, and 7B2-specific neuropeptide. For clinical purposes, it is necessary to have a biochemical marker that can be measured in blood. Lactate, although a primary marker of anaerobic metabolism, and CK-BB values, calculated from the arterio-internal jugular venous difference, appear to correlate with periods of ischemia during ECC. S-100 protein levels have been shown to correlate with duration of ECC, and when combined with NSE values, could be used to identify patients with CNS dysfunction after cardiac surgery. The use of NSE may be limited by its presence in erythrocytes and platelets because the high levels that can result from hemolysis can render it less specific. Although recently introduced, S-100 protein may have the potential to be a valuable marker for CNS dysfunction after ECC.
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PMID:Markers of cerebral ischemia after cardiac surgery. 863 77

In order to achieve a better understanding of the pathophysiology of ischemic white matter lesions, oligodendrocytic degeneration and subsequent proliferation were examined in the mouse model of middle cerebral artery occlusion. In situ hybridization histochemistry for proteolipid protein messenger RNA was employed as a sensitive and specific marker of oligodendrocytes, and immunohistochemistry for myelin basic protein was used as a compact myelin marker. Immunohistochemistry for microtubule-associated protein 2 and albumin was employed to monitor neuronal degeneration and the breakdown of the blood brain barrier, respectively. In the ischemic core of the caudoputamen, the immunoreactivity for microtubule-associated protein 2 disappeared and massive albumin extravasation occurred several hours after vessel occlusion, while proteolipid protein messenger RNA signals remained relatively strong at this time. The messenger RNA signals began to attenuate 12 h after ischemia and were hardly detectable 24 h after ischemia in the whole ischemic lesion. In situ end-labeling of fragmented DNA showed some cells with proteolipid protein messenger RNAs to have DNA fragmentation at this period. In contrast to proteolipid protein messenger RNA signals, the immunoreactivity for myelin basic protein was detected as long as five days after ischemia. An apparent increase in the cells possessing strong proteolipid protein messenger RNA signals was found five days after ischemia, mainly in the corpus callosum and the cortex bordering the infarcted areas. A double simultaneous procedure with in situ hybridization for proteolipid protein messenger RNA and immunohistochemistry for glial fibrillary acid protein or lectin histochemistry for macrophages/microglia showed proliferating oligodendrocytes to be co-localized with reactive astrocytes and macrophages/microglia. These findings show that oligodendrocytic damage occurred following ischemic neuronal damage and the breakdown of the blood brain barrier, but preceded the breakdown of myelin proteins in the ischemic lesion, that an apoptosis-like process was involved in ischemic oligodendrocytic death, and that surviving oligodendrocytes responded and proliferated in the outer border of the infarcted area.
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PMID:Ischemic damage and subsequent proliferation of oligodendrocytes in focal cerebral ischemia. 907 Jul 57

Immune mechanisms contribute to cerebral ischemic injury. Therapeutic immunosuppressive options are limited due to systemic side effects. We attempted to achieve immunosuppression in the brain through oral tolerance to myelin basic protein (MBP). Lewis rats were fed low-dose bovine MBP or ovalbumin (1 mg, five times) before 3 h of middle cerebral artery occlusion (MCAO). A third group of animals was sensitized to MBP but did not survive the post-stroke period. Infarct size at 24 and 96 h after ischemia was significantly less in tolerized animals. Tolerance to MBP was confirmed in vivo by a decrease in delayed-type hypersensitivity to MBP. Systemic immune responses, characterized in vitro by spleen cell proliferation to Con A, lipopolysaccharide, and MBP, again confirmed antigen-specific immunologic tolerance. Immunohistochemistry revealed transforming growth factor beta1 production by T cells in the brains of tolerized but not control animals. Systemic transforming growth factor beta1 levels were equivalent in both groups. Corticosterone levels 24 h after surgery were elevated in all sham-operated animals and ischemic control animals but not in ischemic tolerized animals. These results demonstrate that antigen-specific modulation of the immune response decreases infarct size after focal cerebral ischemia and that sensitization to the same antigen may actually worsen outcome.
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PMID:Immunologic tolerance to myelin basic protein decreases stroke size after transient focal cerebral ischemia. 938 Jul 27

We have determined the effects of the calpain inhibitors AK275 and AK295 upon purified m-calpain and calcium-mediated degradation of neurofilament protein (NFP) in rat spinal cord in vitro. After incubation, the soluble radioactivity and/or extent of myelin basic protein (MBP) or NFP degradation was determined. Fifty percent of caseinolytic activity was inhibited by both inhibitors at 0.6 microM concentration, while more than 90% inhibition was seen at 1.6 microM. In contrast, 37% and 64% inhibition of MBP degradation was seen with AK295 and AK275, respectively, at 10 microM concentration. The extent of NFP degradation in spinal cord was quantified from immunoblot enhanced chemiluminescence. The calcium-mediated breakdown of NFP was inhibited by both AK275 and AK295, and the inhibition was dose-dependent. A 50% inhibition of NFP degradation was seen with AK295 at 10 microM and was almost completely inhibited at 25-50 microM. AK295 was slightly more potent than AK275. These studies suggest that these potent calpain inhibitors may be used therapeutically to provide neuroprotection in vivo in experimental central nervous system trauma and ischemia.
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PMID:New inhibitors of calpain prevent degradation of cytoskeletal and myelin proteins in spinal cord in vitro. 946 75

The excitatory neurotransmitter glutamate is released from axons and glia under hypoxic/ischemic conditions. In vitro, oligodendrocytes (OLs) express non-NMDA glutamate receptors (GluRs) and are susceptible to GluR-mediated excitotoxicity. We evaluated the role of GluR-mediated OL excitotoxicity in hypoxic/ischemic white matter injury in the developing brain. Hypoxic/ischemic white matter injury is thought to mediate periventricular leukomalacia, an age-dependent white matter lesion seen in preterm infants and a common antecedent to cerebral palsy. Hypoxia/ischemia in rat pups at postnatal day 7 (P7) produced selective white matter lesions and OL death. Furthermore, OLs in pericallosal white matter express non-NMDA GluRs at P7. Unilateral carotid ligation in combination with hypoxia (6% O(2) for 1 hr) resulted in selective, subcortical white matter injury with a marked ipsilateral decrease in immature and myelin basic protein-expressing OLs that was also significantly attenuated by 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2,3-dione (NBQX). Intracerebral AMPA demonstrated greater susceptibility to OL injury at P7 than in younger or older pups, and this was attenuated by systemic pretreatment with the AMPA antagonist NBQX. These results indicate a parallel, maturation-dependent susceptibility of immature OLs to AMPA and hypoxia/ischemia. The protective efficacy of NBQX suggests a role for glutamate receptor-mediated excitotoxic OL injury in immature white matter in vivo.
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PMID:NBQX attenuates excitotoxic injury in developing white matter. 1112 1

Insulin-like growth factor-1 (IGF-1) is known to be important for oligodendrocyte survival and myelination. In the current study, the authors examined the hypothesis that exogenous IGF-1 could reduce postischemic white matter injury. Bilateral brain injury was induced in near-term fetal sheep by 30 minutes of reversible carotid artery occlusion. Ninety minutes after ischemia, either vehicle (n = 8) or a single dose of 3 microg IGF-1 (n = 9) was infused intracerebroventricularly over 1 hour. White matter changes were assessed after 4 days recovery in the parasagittal intragyral white matter and underlying corona radiata. Proteolipid protein (PLP) mRNA staining was used to identify bioactive oligodendrocytes. Glial fibrillary acidic protein (GFAP) and isolectin B-4 immunoreactivity were used to label astrocytes and microglia, respectively. Myelin basic protein (MBP) density and the area of the intragyral white matter tracts were determined by image analysis. Insulin-like growth factor-1 treatment was associated with significantly reduced loss of oligodendrocytes in the intragyral white matter (P < 0.05), with improved MBP density (P < 0.05), reduced tissue swelling, and increased numbers of GFAP and isolectin B-4 positive cells compared with vehicle treatment. After ischemia there was a close association of PLP mRNA labeled cells with reactive astrocytes and macrophages/microglia. In conclusion, IGF-1 can prevent delayed, postischemic oligodendrocyte cell loss and associated demyelination.
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PMID:Insulin-like growth factor-1 reduces postischemic white matter injury in fetal sheep. 1133 59

Deleterious processes of extracellular proteolysis may contribute to the progression of tissue damage after acute brain injury. We recently showed that matrix metalloproteinase-9 (MMP-9) knock-out mice were protected against ischemic and traumatic brain injury. In this study, we examined the mechanisms involved by focusing on relevant MMP-9 substrates in blood-brain barrier, matrix, and white matter. MMP-9 knock-out and wild-type mice were subjected to transient focal ischemia. MMP-9 levels increased after ischemia in wild-type brain, with expression primarily present in vascular endothelium. Western blots showed that the blood-brain barrier-associated protein and MMP-9 substrate zonae occludens-1 was degraded after ischemia, but this was reduced in knock-out mice. There were no detectable changes in another blood-brain barrier-associated protein, occludin. Correspondingly, blood-brain barrier disruption assessed via Evans Blue leakage was significantly attenuated in MMP-9 knock-out mice compared with wild types. In white matter, ischemic degradation of the MMP-9 substrate myelin basic protein was significantly reduced in knock-out mice compared with wild types, whereas there was no degradation of other myelin proteins that are not MMP substrates (proteolipid protein and DM20). There were no detectable changes in the ubiquitous structural protein actin or the extracellular matrix protein laminin. Finally, 24 hr lesion volumes were significantly reduced in knock-out mice compared with wild types. These data demonstrate that the protective effects of MMP-9 gene knock-out after transient focal ischemia may be mediated by reduced proteolytic degradation of critical blood-brain barrier and white matter components.
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PMID:Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia. 1156 62

Phosphorylation of cyclic adenosine monophosphate (AMP) response element binding protein (CREB) was examined immunohistochemically in the corpus callosum of the rat brain at various time points after 90-minute focal cerebral ischemia. Focal ischemia was induced by occlusion of the middle cerebral artery (MCA) using the intraluminal suture method. Sham animals showed that numerous oligodendrocytes (OLGs) constitutively express unphosphorylated CREB. Local cerebral blood flow (lCBF) measured by the 14C-iodoantipyrine method was reduced from 44.2 +/- 15.4 (mL 100 g(-1) min(-1)) to 18.4 +/- 3.8 and from 53.9 +/- 14.4 to 4.8 +/- 4.5 in the medial and the lateral regions of the corpus callosum, respectively, during MCA occlusion (MCAO). After release of the MCAO, lCBF recovered to the control level in each region. The medial region of the corpus callosum showed a marked increase in phosphorylated CREB-positive OLGs at 3.5 hours of recirculation, and it remained increased until 2 weeks of recirculation as it gradually declined. The activation of CREB phosphorylation in the OLGs was accompanied by expression of antiapoptotic protein bcl-2, normal staining with cresyl violet, and negative TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) staining. Myelination detected by immunostaining with anti-myelin basic protein (MBP) antibody and anti-myelin associated glycoprotein (MAG) antibody remained normal in the medial region of the corpus callosum. The lateral region of the corpus callosum showed a significant but only transient increase in phosphorylated CREB-positive OLGs at 3.5 hours of recirculation, which was followed by a rapid decrease during the subsequent recirculation period. Expression of bcl-2 was suppressed in this region, and demyelination became apparent. These findings suggest that signal transduction through CREB phosphorylation may be closely associated with survival of OLGs and maintenance of myelination in the corpus callosum after cerebral ischemia.
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PMID:Phosphorylation of cyclic adenosine monophosphate response element binding protein in oligodendrocytes in the corpus callosum after focal cerebral ischemia in the rat. 1159 95


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