Journal
NEUROBIOLOGY OF DISEASE
Volume 33, Issue 3, Pages 509-517Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2008.12.010
Keywords
Apoptosis; HIF-1 alpha; MCAO; siRNA
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Funding
- National Natural Science Foundation of China [30672157]
- Graduate Student Foundation of China [20050001123]
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Hypoxia-inducible factor-1 (HIF-1) plays an essential role in cerebral ischemia as a proapoptotic factor. We hypothesized that HIF-1 alpha siRNA can protect the brain from ischemic damage by inhibiting HIF-1 alpha induced apoptotic pathway at the RNA level in a rat focal ischemic model. Results showed that treatment with HIF-1 alpha siRNA reduced the infarct volume, decreased mortality, improved neurological deficits and reduced Evans blue extravasation. The expression of HIF-1 alpha mRNA (Real-Time PCR) and protein were significantly silenced and the immunohistochemistry and Western blot revealed the suppression of HIF-1 alpha, VEGF, p53 and Caspase-3. Double fluorescence labeling showed HIF-1 alpha positive immunoreactive materials were partly colocalized with NeuN, p53 and Caspase-3 in the injured cerebral cortex. This study showed that HIF-1 alpha siRNA may protect the ischemic-reperfused neurons in vivo via inhibition of HIF-1 alpha, its downstream VEGF and other apoptotic-related proteins such as p53 and Caspase-3 and may have potentials for the early treatment of ischemic cerebral stroke. (C) 2008 Published by Elsevier Inc.
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