Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 33, Issue 4, Pages 524-531Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/jcbfm.2012.193
Keywords
acriflavine; edema; HIF-1 alpha; hypothermia; preconditioning; traumatic brain injury
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Funding
- Professor Jashovam Shani Fund
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Heat acclimation (HA), a well-established preconditioning model, confers neuroprotection in rodent models of traumatic brain injury (TBI). It increases neuroprotective factors, among them is hypoxia-inducible factor 1 alpha (HIF-1 alpha), which is important in the response to postinjury ischemia. However, little is known about the role of HIF-1a in TBI and its contribution to the establishment of the HA protecting phenotype. Therefore, we aimed to explore HIF-1 alpha role in TBI defense mechanisms as well as in HA-induced neuroprotection. Acriflavine was used to inhibit HIF-1 in injured normothermic (NT) or HA mice. After TBI, we evaluated motor function recovery, lesion volume, edema formation, and body temperature as well as HIF-1 downstream transcription targets, such as glucose transporter 1 (GLUT1), vascular endothelial growth factor, and aquaporin 4. We found that HIF-1 inhibition resulted in deterioration of motor function, increased lesion volume, hypothermia, and reduced edema formation. All these parameters were significantly different in the HA mice. Western blot analysis and enzyme-linked immunosorbent assay showed reduced levels of all HIF-1 downstream targets in HA mice, however, only GLUT1 was downregulated in NT mice. We conclude that HIF-1 is a key mediator in both spontaneous recovery and HA-induced neuroprotection after TBI. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 524-531; doi:10.1038/jcbfm.2012.193; published online 2 January 2013
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