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

Exposure of primary cultures of neonatal rat cortical astrocytes to bacterial lipopolysaccharide (LPS) results in the appearance of nitric oxide synthase (NOS) activity. The induction of NOS, which is blocked by actinomycin D, is directly related to the duration of exposure and dose of LPS, and a 2-hr pulse can induce enzyme activity. Cytosol from LPS-treated astrocyte cultures, but not from control cultures, produces a Ca(2+)-independent conversion of L-arginine to L-citrulline that can be completely blocked by the specific NOS inhibitor NG-monomethyl-L-arginine. The induced NOS activity exhibits an apparent Km of 16.5 microM for L-arginine and is dependent on NADPH, FAD, and tetrahydrobiopterin. LPS also induces NOS in C6 glioma cells and microglial cultures but not in cultured cortical neurons. The expression of NOS in astrocytes and microglial cells has been confirmed by immunocytochemical staining using an antibody to the inducible NOS of mouse macrophages and by histochemical staining for NADPH diaphorase activity. We conclude that glial cells of the central nervous system can express an inducible form of NOS similar to the inducible NOS of macrophages. Inducible NOS in glia may, by generating nitric oxide, contribute to the neuronal damage associated with cerebral ischemia and/or demyelinating diseases.
 ...
PMID:Induction of calcium-independent nitric oxide synthase activity in primary rat glial cultures. 127 98

We have characterized the induction of the mitogen-inducible form of cyclo-oxygenase, COX-2, during focal cerebral ischemia following permanent middle cerebral artery occlusion (MCAO) in the rat. Marked unilateral induction of COX-2 mRNA was detected in ischemic regions ipsilateral to the occlusion. A significant increase in COX-2 mRNA was detected in "core" and "penumbra" regions of the cerebral cortex between 4 and 24 h after occlusion; this was most marked at 4 h in the penumbra region, in which a 19-fold increase above untreated control levels was detected. A smaller but significant induction was also detected at 4 h in the caudate. A correlation was demonstrated between the extent of COX-2 mRNA induction in cortical regions at 4 h and the severity of tissue damage subsequently detected at 24 h post MCAO. MK-801 significantly attenuated the induction of COX-2 mRNA in the penumbra region at 4 h. The demonstration of COX-2 induction following experimental ischemia highlights the importance of this reaction and its products and by-products, for example, free radicals, in the tissue response to this insult.
 ...
PMID:Cyclo-oxygenase-2 messenger RNA induction in focal cerebral ischemia. 889 13

Transgenic technology provides a powerful means of studying gene regulation and specific gene function with complex mammalian systems. In this study, the authors exploited the specific and discrete neuronal expression pattern mediated by promoter 1 of the Lmo-1 gene to study the neuroprotective effects of the inducible form of heat shock protein 70kD (hsp70i) in primary hippocampal cultures in a mouse model of global cerebral ischemia. Targeting expression of hsp70i to hippocampal neurons protected these cells significantly from toxic levels of glutamate and oxidative stress (for example, exposure to 10 micromol/L free iron produced a 26% increase in lactate dehydrogenase release from neurons cultured from wild-type mice, but a 7% increase in neurons cultured from hsp70i transgenic mice). Bilateral carotid occlusion (25 minutes) produced significantly less neuronal damage in the caudate nucleus and posterior thalamus in hsp70i transgenic mice than in wild-type littermates (for example, 21% +/- 9.3% and 12.5% +/- 9.0% neuronal damage in lateral caudate nucleus of wild-type and hsp70i transgenic mice, respectively, P < 0.05). The current study highlights the utility of targeted expression of transgenes of interest in cerebral ischemia and demonstrates that expression of hsp70i alone is sufficient to mediate the protection of primary neurons from denaturing stress and that expression of human hsp70i in vivo plays crucial role in determining the fate of neurons after ischemic challenge.
 ...
PMID:Targeting expression of hsp70i to discrete neuronal populations using the Lmo-1 promoter: assessment of the neuroprotective effects of hsp70i in vivo and in vitro. 1148 33

Heat shock protein 70 (Hsp70) is induced in cells by a variety of stress conditions, is known to be cytoprotective, and has been proposed to be neuroprotective during brain ischemia. A recently developed mouse model of 12-min global cerebral ischemia by bilateral common carotid artery occlusion with artificial ventilation and bilateral monitoring of regional cerebral blood flow by laser Doppler was applied. We examined the expression and possible neuroprotective role of the inducible form of Hsp70 in the mouse brain following global cerebral ischemia. Ischemia induced a marked expression of Hsp70 in the ischemia vulnerable CA1-CA3 region of the hippocampus. Intraischemic hypothermia (33 degrees C) prevented cell damage without noticeable expression of Hsp70. A transgenic mouse overexpressing Hsp70 was subjected to 12 min of global cerebral ischemia, and the brain damage was evaluated after 4 days. No neuroprotection of ischemia-induced brain damage in hippocampus, striatum, cortex or thalamus was found in Hsp70 transgenic animals compared with wild-type littermate mice. We suggest that overexpression of Hsp70 following cerebral ischemia is an indicator of cell stress. Also, constitutively overexpression of Hsp70 is insufficient to effectively influence cell death after global cerebral ischemia in the mouse.
 ...
PMID:Lack of neuroprotection by heat shock protein 70 overexpression in a mouse model of global cerebral ischemia. 1457 3

In this work, we report our study of protein expression in rat peri-infarct tissue, 48 h after the induction of permanent focal cerebral ischemia. Two proteomic approaches, gel electrophoresis with mass spectrometry and combined fractional diagonal chromatography (COFRADIC), were performed using tissue samples from the periphery of the induced cerebral ischemic lesions, using tissue from the contra-lateral hemisphere as a control. Several protein spots (3408) were identified by gel electrophoresis, and 11 showed significant differences in expression between peri-infarct and contra-lateral tissues (at least 3-fold, p < 0.05). Using COFRADIC, 5412 proteins were identified, with 72 showing a difference in expression. Apart from blood-related proteins (such as serum albumin), both techniques showed that the 70 kDa family of heat shock proteins were highly expressed in the peri-infarct tissue. Further studies by 1D and 2D western blotting and immunohistochemistry revealed that only one member of this family (the inducible form, HSP72 or HSP70i) is specifically expressed by the peri-infarct tissue, while the majority of this family (the constitutive form, HSC70 or HSP70c) is expressed in the whole brain. Our data support that HSP72 is a suitable biomarker of peri-infarct tissue in the ischemic brain.
 ...
PMID:Study of Protein Expression in Peri-Infarct Tissue after Cerebral Ischemia. 2615 30