Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The local cerebral glucose utilization (CMRglc) in the damaged rat hippocampal CA1 subfield increases 7 days after 10 min of cerebral ischemia. We have used the N-methyl-D-aspartate antagonist (NMDA antagonist) ketamine in rats 7 days after sham operation or cerebral ischemia to determine whether the elevated postischemic CMRglc of the CA1 subfield is due to long-lasting hyperexcitation of surviving or injured neurons, or, alternatively, to the metabolism of other cell types. The autoradiographic data were interpreted with the aid of histochemical analysis of the postischemic hippocampal cell changes. Anesthetic doses of ketamine significantly reduced the CMRglc in the CA1 strata oriens, pyramidale and radiatum of sham-operated rats, while the postischemic increases in CMRglc in these hippocampal CA1 strata were not affected by ketamine. In addition, there were ketamine-induced increases in the CMRglc of the CA1 stratum lacunosum moleculare of both sham-operated and postischemic rats. The immunoreactivity of the microtubule-associated protein 2 (MAP2), a postsynaptic protein marker, was decreased markedly in the CA1 subfield in postischemic rats, while the presynaptic protein marker, synaptophysin, remained the same in sham-operated and postischemic rats. The glial fibrillary acidic protein (GFAP) immunoreactivity of astrocytes raised markedly in the ischemically damaged CA1 subfield. Although it could be demonstrated that presynaptic terminals remain intact in the postischemic damaged CA1 subfield, the lacking ketamine effect on CA1 pyramidal neurons indicated that the increase in CMRglc in this brain area is not due to postsynaptic neural hyperexcitation, but probably has to be attributed to astrocytes activated by neuronal damage.
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PMID:Activated astrocytes, but not pyramidal cells, increase glucose utilization in rat hippocampal CA1 subfield after ischemia. 143 24

Plasticity in the central nervous system has been demonstrated using lesions of the hippocampus and rhinal cortex but has not been well studied after cerebral ischemia. Focal cerebral ischemia creates an area of infarction that is surrounded by neuronal tissue that may respond to nearby damage by creating new synapses. To determine if synaptogenesis occurs, antibodies to synaptophysin, a calcium-binding protein found on synaptic vesicles, were used with immunohistochemical techniques to assess the level of synaptophysin immunoreactivity as a measure of changes in the number of synapses. Cerebral ischemia was induced in hypertensive rats by permanently occluding the distal middle cerebral artery and ipsilateral common carotid artery. After 2 months recovery, the animals were perfused and the brains removed for immunohistochemical processing and evaluation. When comparing the cortex surrounding the infarcted area to similar areas on the contralateral side of the brain, the infarcted side had increased levels of anti-synaptophysin like activity that are statistically significant. We hypothesize that this increase in synaptophysin immunoreactivity is due to an increase in synapses in the cortex surrounding an area of infarction and supports the hypothesis of plasticity in the cortex following cerebral infarction.
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PMID:Increase in synaptophysin immunoreactivity following cortical infarction. 148 Mar 19

We assessed the chronological change of the expression of synaptophysin, an integral glycoprotein on the presynaptic vesicles, after a transient cerebral ischemic insult in the rat. The ischemic lesion was consistently localized in the dorsolateral part of the striatum, which was clearly visualized by a depletion of calcineurin immunostaining or increases of immunoreactivities for glial fibrillary acidic protein and tyrosine hydroxylase. Immunoreactivity for synaptophysin was transiently increased in the ischemic lesions from 3 to 7 days after cerebral ischemia. Thereafter, synaptophysin immunostaining in the damaged areas gradually decreased and finally almost disappeared one month after surgery. Because synaptophysin is located in the presynaptic vesicle, and thought to be involved in presynaptic functions such as vesicle-membrane fusion and release of neurotransmitters, present findings suggest that loss of the postsynaptic site after ischemic insult induces a transient increase of the presynaptic functions, followed by a decrease of functional presynaptic activity or trans-synaptic retrograde degeneration of axon terminals.
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PMID:Changes of immunoreactivity for synaptophysin ('protein p38') following a transient cerebral ischemia in the rat striatum. 810 40

Focal cerebral ischemia creates an area of infarction that is surrounded by neuronal tissue that may respond to nearby damage by creating neurite growth. To determine if axonal sprouting occurs after infarction, antibodies to growth associated protein MW 43,000 (GAP-43), a protein expressed on axonal growth cones, were used to assess the level of GAP-43 immunoreactivity as a measure of sprouting. Cerebral ischemia was induced in spontaneously hypertensive rats by permanently occluding the distal middle cerebral artery and ipsilateral common carotid artery. After 1 week of recovery, the animals were perfused, the brains removed, processed, and optical densities of the immunoreaction were measured. The cortex surrounding the infarcted area had increased optical densities (mean +/- S.D. = 14.2% +/- 5.5) compared to the optical density values measured in similar areas in the contralateral hemisphere (mean +/- S.D. = 6.0% +/- 3.3), a 136% increase that is statistically significant, P < 0.05 Student's t-test. We hypothesize that this increase in GAP-43 reaction product is due to axonal sprouting in the cortex surrounding an area of infarction. These data, coupled with previous work examining synaptophysin levels after cortical infarction, support the hypothesis of sprouting and synaptogenesis in the cortex following cerebral infarction.
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PMID:Acute increase in expression of growth associated protein GAP-43 following cortical ischemia in rat. 812 36

Changes in drebrin, MAP2 (postsynaptic marker) and synaptophysin (presynaptic marker) in rat brains were examined after 20 min of transient cerebral ischemia. Immunoreactivity for drebrin and MAP2 in hippocampus CA1 area decreased 7 days after ischemia. The immunoreactivity for debrin in stratum lucidum of hippocampus CA3 area increased 7 days after ischemia. Sodium dodecyl sulfate gel electrophoresis and immunoblot procedures using an antibody to drebrin, MAP2 and synaptophysin were carried out. The levels of drebrin and MAP2 in hippocampus decreased significantly 4 hours and 7 days after recirculation. In contrast, the level of synaptophysin was unchanged. The levels of each protein in cerebral cortex showed no significant changes. The changes after ischemia seemed to occur at the same time both in the dendritic spines and in their shafts, and the increase of the immunoreactivity for drebrin in CA3 might suggest the change of cytoskeletal protein synthesis in survived neurons.
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PMID:[The changes of central nervous synapses after transient cerebral ischemia]. 858 59

Plasticity in the central nervous system after cerebral ischemia is a controversial issue; focal cerebral ischemia produces an area of infarction that is surrounded by neurons that may respond to nearby damage by creating new synapses. In the present study the expression of the postsynaptic microtubule-associated protein 2 (MAP2) and the presynaptic marker protein, synaptophysin, was investigated by immunocytochemical techniques in the CA1 sector of hippocampus and in cerebellum of rats made ischemic by bilateral clamping of common carotid arteries and reperfused for 7 and 30 days. In addition, ischemia-induced behavioral alterations were also evaluated after 7 and 30 days of reperfusion. The present study demonstrates a decreased postsynaptic MAP2 immunoreactivity, representative of neuronal loss, particularly in CA1 sector of hippocampus and in cerebellum of ischemic rats reperfused for 7 days. After 30 days of reperfusion, MAP2 immunostaining was similar to control. In the same brain sections an increased presynaptic synaptophysin immunoreactivity has been observed only after 30 days of reperfusion. These data suggest compensatory regenerative changes associated with synaptic remodelling and are supported by behavioral recovery observed under the same experimental conditions.
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PMID:MAP2, synaptophysin immunostaining in rat brain and behavioral modifications after cerebral postischemic reperfusion. 944 83

The aim of the present study was to evaluate the use of the endogenous neuronal compound N-acetylaspartate (NAA) as a marker of neuronal damage after focal cerebral ischemia in mice. After occlusion of the middle cerebral artery (MCAO) the ischemic cortex was sampled, guided by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and the NAA concentration was measured by high-pressure liquid chromatography (HPLC). Conventional histology and immunohistological methods using antibodies against neuron-specific enolase (NSE), neurofilaments (NF), synaptophysin, glial fibrillary acidic protein (GFAP), and carbodiamide-linked NAA and N-acetylaspartylglutamate (NAAG). The level of NAA rapidly declined to 50% and 20% of control levels in infarcted tissue after 6 hours and 24 hours, respectively. No further decrease was observed during the observation period of 1 week. Within the first 6 hours the number of normal-appearing neurons in the infarcted cortical tissue decreased to 70% of control, of which the majority were eosinophilic. After 24 hours almost no normal-appearing neurons were seen. The number of eosinophilic neurons decreased steadily to virtually zero after 7 days. The number of immunopositive cells in the NSE, NF, and synaptophysin staining within the infarct was progressively reduced, and after 3 to 7 days the immunoreactions were confined to discrete granulomatous structures in the center of the infarct, which otherwise was infested with macrophages. This granulomatous material also stained positive for NAA. The number of cells with positive GFAP immunoreactions progressively increased in the circumference of the infarct. They also showed increased immunoreaction against NAA and NSE. The study shows that the level of NAA 7 days after ischemia does not decline to zero but remains at 10% to 20% of control values. The fact NAA is trapped in cell debris and NAA immunoreactivity is observed in the peri-infarct areas restricts its use as a marker of neuronal density.
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PMID:Correlation between N-acetylaspartate levels and histopathologic changes in cortical infarcts of mice after middle cerebral artery occlusion. 1082 28

Bone marrow stromal cells (MSCs) are an excellent source of cells for treating a variety of central nervous system diseases. In this study, we report the efficient induction of committed neural progenitor cells from rat and human MSCs (NS-MSCs) by introduction of cells with the intracellular domain of Notch-1 followed by growth in the free-floating culture system. NS-MSCs successfully formed spheres, in which cells highly expressed the neural precursor cell markers. The commitment of spheres to neural lineage cells was confirmed by their successful differentiation into neuronal cells when exposed to a differentiation medium. To determine the therapeutic potential of NS-MSCs, cells were transplanted into the cortex and striatum in a rat model of focal cerebral ischemia. The survival, distribution, and integration of NS-MSCs in the host brain were very high, and at day 100, grafted NS-MSCs were positive for dopaminergic, glutamatergic, and gamma-amino butyric acid(GABA)ergic neuronal markers. They extended long neurites for nearly 6.3 mm and many of these expressed synaptophysin. Significant behavioral recovery was also observed in limb-placing and water-maze tests. These suggest a high potential for this MSC approach in the replenishment of neural cells for stroke and for a wide range of neurodegenerative conditions that require various types of neural cells.
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PMID:Committed neural progenitor cells derived from genetically modified bone marrow stromal cells ameliorate deficits in a rat model of stroke. 1943 12

Cerebral ischemia induces cortical function reorganization and neocortical neurogenesis in the cerebral hemisphere. However, whether the cerebellum undergoes corresponding dynamic change after cerebral injury has not been determined. We investigated the characteristics of cell proliferation and synaptogenesis in the cerebellum after focal cerebral ischemia. After induction of focal cerebral ischemia in rats, bromodeoxyuridine (BrdU, 100 mg/kg, intraperitoneally, daily) was administered for 5 days. Brain sections were analyzed using immunohistochemistry at days 7, 14, and 28. BrdU+ cells and Iba-1+ cells were counted, and cerebellar synaptophysin immunoreactivity was quantitatively analyzed. Rats with cerebral ischemia showed increased numbers of BrdU+ cells in the cerebellum at day 28 compared to sham-operated rats. Neither neuronal markers nor GABAergic markers were co-labeled with BrdU+ cells, suggesting that none of the proliferating cells contributed to neurogenesis. Instead, the number of Iba-1+ cells in the cerebellum was increased, which suggests that microglia are activated in the cerebellum after cerebral ischemia. The optical density of synaptophysin in the cerebellum of rats with cerebral ischemia was significantly increased in the molecular and granular layers at days 7 and 14. Cerebellar synaptophysin expression was significantly correlated with cerebellar cell proliferation. This study shows that the cerebellum undergoes specific and dynamic changes at the cellular level after focal cerebral ischemia, including cell proliferation and synaptogenesis.
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PMID:Cell proliferation and synaptogenesis in the cerebellum after focal cerebral ischemia. 1948 98

Glial scarring is traditionally thought to be detrimental after stroke. But emerging studies now suggest that reactive astrocytes may also contribute to neurovascular remodeling. Here, we assessed the effects and mechanisms of metabolic inhibition of reactive astrocytes in a mouse model of stroke recovery. Five days after stroke onset, astrocytes were metabolically inhibited with fluorocitrate (FC, 1 nmol). Markers of reactive astrocytes (glial fibrillary acidic protein (GFAP), HMGB1), markers of neurovascular remodeling (CD31, synaptophysin, PSD95), and behavioral outcomes (neuroscore, rotarod latency) were quantified from 1 to 14 days. As expected, focal cerebral ischemia induced significant neurological deficits in mice. But over the course of 14 days after stroke onset, a steady improvement in neuroscore and rotarod latencies were observed as the mice spontaneously recovered. Reactive astrocytes coexpressing GFAP and HMGB1 increased in peri-infarct cortex from 1 to 14 days after cerebral ischemia in parallel with an increase in the neurovascular remodeling markers CD31, synaptophysin, and PSD95. Compared with stroke-only controls, FC-treated mice demonstrated a significant decrease in HMGB1-positive reactive astrocytes and neurovascular remodeling, as well as a corresponding worsening of behavioral recovery. Our results suggest that reactive astrocytes in peri-infarct cortex may promote neurovascular remodeling, and these glial responses may aid functional recovery after stroke.
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PMID:Inhibition of reactive astrocytes with fluorocitrate retards neurovascular remodeling and recovery after focal cerebral ischemia in mice. 1999 16


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