Heat acclimation provides sustained improvement in functional recovery and attenuates apoptosis after traumatic brain injury

Gali Umschwief, Na'Ama A. Shein, Alexander G. Alexandrovich, Victoria Trembovler, Michal Horowitz, Esther Shohami*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Heat acclimation (HA) offers functional neuroprotection in mice after traumatic brain injury (TBI). This study further characterizes endogenous neuroprotection acquired by HA (341°C, 30 d) after TBI. We establish here the ability of HA to induce sustained functional benefits and to reduce activation of apoptotic pathways. Neurobehavioral recovery, assessed by the Neurological Severity Score, was greater in HA mice up to 8 days after injury as compared with normothermic controls (P0.05) and lesion volume was also smaller in the HA group (P0.05). Reduced apoptotic cell death in HA mice was confirmed using caspase-3 activity measurements and immunohistochemistry. To investigate the underlying molecular pathways, expression levels of intrinsic apoptotic pathway-related proteins were examined. HA mice displayed higher mitochondrial levels of antiapoptotic Bcl-xL, accompanied by lower proapoptotic Bad levels and decreased cytochrome c release, suggesting a higher apoptotic threshold. Taken together with our previous reports, indicating increased Akt phosphorylation and antioxidative capacity, alongside with reduced tumor necrosis α levels after TBI in HA animals, the current results support the involvement of an antiapoptotic effect in HA-induced neuroprotection. Current results warrant further study as TBI-induced apoptosis may persist over weeks after injury, possibly providing a target for belated therapeutic intervention.

Original languageAmerican English
Pages (from-to)616-627
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume30
Issue number3
DOIs
StatePublished - Mar 2010

Keywords

  • Bad
  • Bcl-xL
  • Caspase-3
  • Cytochrome c
  • Neuroprotection

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