Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xenon preconditioning induces tolerance to the consequences of an injurious stimulus such as cerebral ischaemia. There have been surprisingly few studies investigating gender difference in the efficacy of pharmacological preconditioning, despite the known ability of oestradiol to exert neuroprotectant activity. We explored this paradigm using a mouse model of transient middle cerebral artery occlusion. C57BL/6 mice both male and female received either 2 h of 70% xenon (preconditioning) or 70% nitrogen (control) balanced with oxygen. Twenty-four hours later animals underwent 1 h of middle cerebral artery occlusion and then allowed to recover. After a further 24 h, functional neurological outcome and cerebral infarct size were evaluated. Western blotting was used to detect activity of signalling pathways involving hypoxia-inducible factor (HIF)-1alpha and phospho-Akt for the preconditioning effect. Both xenon preconditioned male and females showed improved functional outcome on focal deficit scales (P<0.05). Cerebral infarct volumes were significantly reduced in both xenon treated male and females (P<0.01). There was no significant difference between the male and female cohorts. HIF-1alpha and phospho-Akt were quantitatively upregulated in both sexes. Our data suggested that xenon preconditioning improved histological and neurological functional outcome in both gender in a stroke model of mice.
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PMID:Xenon preconditioning confers neuroprotection regardless of gender in a mouse model of transient middle cerebral artery occlusion. 1989 74

Hypoxia-inducible factor-1alpha/beta (HIF-1alpha/beta) is a heterodimeric transcriptional activator that mediates gene expression in response to hypoxia. HIF-1alpha has been noted as an effective therapeutic target for ischemic diseases such as myocardiac infarction, stroke and cancer. By using a yeast two-hybrid system and a random peptide library, we found a 16-mer peptide named F29 that directly interacts with the bHLH-PAS domain of HIF-1alpha. We found that F29 facilitates the interaction of the HIF-1alpha/beta heterodimer with its target DNA sequence, hypoxia-responsive element (HRE). The transient transfection of an F29-expressing plasmid increases the expression of both an HRE-driven luciferase gene and the endogenous HIF-1 target gene, vascular endothelial growth factor (VEGF). Taken together, we conclude that F29 increases the DNA-binding ability of HIF-1alpha, leading to increased expression of its target gene VEGF. Our results suggest that F29 can be a lead compound that directly targets HIF-1alpha and increases its activity.
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PMID:The novel peptide F29 facilitates the DNA-binding ability of hypoxia-inducible factor-1alpha. 1994 15

While survival from stroke, traumatic brain and spinal cord injuries, neurodegenerative diseases and hypoxia has improved over the past several years, treatments are limited and impacts of these injuries and diseases to patients, families and society can be devastating. Recovery from these injuries is variable and involves in part an orchestrated angiogenesis and neurogenesis in the neurogenic zones (neurovascular niches) of the CNS. In this focused review the roles of HIF-1alpha mediated responses to hypoxia in CNS neurovascular niches is discussed. Using in vivo and in vitro murine models of sublethal hypoxia we mimicked the variable responses observed in the human population and correlated differences in baseline and hypoxia-induced induction of HIF-1alpha and several downstream signaling components including BDNF, VEGF, SDF-1, TrkB, Nrp-1, CXCR4 and NO with differences in survival as well as endothelial cell and neural stem cell survival and proliferation, providing insight into this important and timely problem and suggesting that optimization of expression levels of some or all of these signaling components may have the potential of maximizing recovery following CNS injury.
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PMID:Modeling the neurovascular niche: implications for recovery from CNS injury. 2008 57


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