Document Detail

Hypoxia-inducible factor 1 is essential for spontaneous recovery from traumatic brain injury and is a key mediator of heat acclimation induced neuroprotection.
MedLine Citation:
PMID:  23281425     Owner:  NLM     Status:  MEDLINE    
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 1α (HIF-1α), which is important in the response to postinjury ischemia. However, little is known about the role of HIF-1α in TBI and its contribution to the establishment of the HA protecting phenotype. Therefore, we aimed to explore HIF-1α 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.
Gali Umschweif; Alexander G Alexandrovich; Victoria Trembovler; Michal Horowitz; Esther Shohami
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Publication Detail:
Type:  Journal Article     Date:  2013-01-02
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  33     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-01     Completed Date:  2013-05-23     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  524-31     Citation Subset:  IM    
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MeSH Terms
Acriflavine / pharmacology
Anti-Infective Agents, Local / pharmacology
Aquaporin 4 / biosynthesis
Brain Edema / metabolism*,  pathology
Brain Injuries / metabolism*,  pathology
Glucose Transporter Type 1 / biosynthesis
Hot Temperature*
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
Nerve Tissue Proteins / metabolism*
Remission, Spontaneous
Reg. No./Substance:
0/Anti-Infective Agents, Local; 0/Aqp4 protein, mouse; 0/Aquaporin 4; 0/Glucose Transporter Type 1; 0/Hif1a protein, mouse; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Nerve Tissue Proteins; 0/Slc2a1 protein, mouse; 1T3A50395T/Acriflavine

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