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)

The brain's response to ischemia, which helps determine clinical outcome after stroke, is regulated partly by competing genetic programs that respectively promote cell survival and delayed cell death. Many genes involved in this response have been identified individually or systematically, providing insights into the molecular basis of ischemic injury and potential targets for therapy. The development of microarray systems for gene expression profiling permits screening of large numbers of genes for possible involvement in biological or pathological processes. Therefore, we used an oligodeoxynucleotide-based microarray consisting of 374 human genes, most implicated previously in apoptosis or related events, to detect alterations in gene expression in the hippocampus of rats subjected to 15 minutes of global cerebral ischemia followed by up to 72 hours of reperfusion. We found 1.7-fold or greater increases in the expression of 57 genes and 1.7-fold or greater decreases in the expression of 34 genes at 4, 24, or 72 hours after ischemia. The number of induced genes increased from 4 to 72 hours, whereas the number of repressed genes decreased. The induced genes included genes involved in protein synthesis, genes mutated in hereditary human diseases, proapoptotic genes, antiapoptotic genes, injury-response genes, receptors, ion channels, and enzymes. We detected transcriptional induction of several genes implicated previously in cerebral ischemia, including ALG2, APP, CASP3, CLU, ERCC3, GADD34, GADD153, IGFBP2, TIAR, VEGF, and VIM, as well as other genes not so implicated. We also found coinduction of several groups of related genes that might represent functional modules within the ischemic neuronal transcriptome, including VEGF and its receptor, NRP1; the IGF1 receptor and the IGF1-binding protein IGFBP2; Rb, the Rb-binding protein E2F1, and the E2F-related transcription factor, TFDP1; the CACNB3 and CACNB4 beta-subunits of the voltage-gated calcium channel; and caspase-3 and its substrates, ACINUS, FEM1, and GSN. To test the hypothesis that genes identified through this approach might have roles in the pathophysiology of cerebral ischemia, we measured expression of the products of two induced genes not heretofore implicated in cerebral ischemia-GRB2, an adapter protein involved in growth-factor signaling pathways, and SMN1, which participates in RNA processing and is deleted in most cases of spinal muscular atrophy. Western analysis showed enhanced expression of both proteins in hippocampus at 24 to 72 hours after ischemia, and SMN1 was localized by immunohistochemistry to hippocampal neurons. These results suggest that microarray analysis of gene expression may be useful for elucidating novel molecular mediators of cell death and survival in the ischemic brain.
 ...
PMID:Microarray analysis of hippocampal gene expression in global cerebral ischemia. 1145 15

Preconditioning (PC) is a phenomenon in which a brief ischemic insult induces tolerance against a subsequent severe ischemic insult. Recent studies showed that cerebral ischemia in adult rat upregulates progenitor cell proliferation in the hippocampal dentate gyrus. We presently evaluated whether PC can also stimulate progenitor cell proliferation in rat brain. Middle cerebral artery was transiently occluded in spontaneously hypertensive rats for 10 min to induce PC and 1h to induce focal ischemia. Progenitor cell proliferation (defined as BrdU(+) cell number) significantly increased after focal ischemia (by 3.9-fold; p<0.05) as well as PC (by 2.7-fold; p<0.05) compared to sham. PC 3 days prior had neither an inhibitory nor an additive effect on focal ischemia-induced progenitor cell proliferation. In both ischemia and PC groups, approximately 45% of the progenitor cells proliferated in week 1 survived to the end of week 3 and approximately 21% of those matured into NeuN(+) neurons. Furthermore, cerebral mRNA expression of the growth factors IGF1, FGF2, TGFbeta1, EGF and PDGF-A was significantly elevated after PC. Thus, we show that the beneficial effects of PC extend beyond providing neuroprotection during the acute phase after ischemia. Induction of growth factor expression and neurogenesis by PC might be a positive adaptation for an efficient repair and plasticity in the event of an ischemic insult.
 ...
PMID:Preconditioning-induced ischemic tolerance stimulates growth factor expression and neurogenesis in adult rat hippocampus. 1615 34

Insulin like growth factor-1 (IGF-1) plays an important role in the proliferation and differentiation of neural progenitor cells. The effects of IGF-1 can be regulated by insulin like growth factor binding protein-3 (IGFBP-3) which can either inhibit or stimulate the proliferation of cells depending on the expression of proteases that can release IGF-1 from IGF1-IGFBP3 complex. Although IGF-1 is essential for the development of brain, both IGFBP-3 and IGF-1 are elevated in the brains of children younger than 6 months of age. Likewise, IGFBP-3 is also upregulated following cerebral ischemia and hypoxia. However, the role of IGFBP-3 in neurogenesis is not clear. Using an in vitro culture system of rat neural progenitor cells, we demonstrate that IGFBP-3 specifically regulates the IGF-1 mediated neural progenitor cell proliferation via down regulation of phospho-Akt, and cyclin D1. In addition, IGFBP-3 also decreased the content of nestin in the neural progenitor cells indicating its potential role in neurogenesis.
 ...
PMID:IGFBP-3 inhibits the proliferation of neural progenitor cells. 2113 51

Ischemic stroke is a leading cause of irreversible brain damages and disabilities. In the past decade, much attention has been focused on exploring effective strategies to promote circuit reorganization and functional recovery post injury. Here, we showed that the expression level of a long non-coding RNA (lncRNA H19) is bilaterally increased in the sensorimotor cortex after a cerebral ischemia induced by middle cerebral artery occlusion (MCAO). Knock down of contralaterally elevated H19 robustly enhanced the midline-crossing sprouting of the intact corticospinal axons in the spinal cord. Furthermore, H19 knockdown mice showed significant improvement on the performance of the food pellet retrieval assay, a skilled, cortical dependent motor task. Mechanistically, lncRNA H19 inhibition increased IGF1R expression and activated IGF1 mediated mTOR pathway. Our research thereby provided novel insights into identifying therapeutic targets for ischemic stroke.
 ...
PMID:Knock down of lncRNA H19 promotes axon sprouting and functional recovery after cerebral ischemic stroke. 3199 Nov 23