title: Altered cytokine expression and sustained hypothermia following traumatic brain injury in heat acclimated mice.
abstract: Long-term exposure to moderate ambient heat (heat acclimation, HA, 30 days at 34+/-1 degrees C) provides protection toward a variety of stressors including traumatic brain injury. As previous studies suggested an anti-inflammatory effect of HA and given the ability of augmented pre-injury anti-inflammatory cytokine expression to harbor neuroprotection and to attenuate early post-injury expression of pro-inflammatory mediators, we hypothesized that HA-induced neuroprotection may involve enhanced pre-injury expression of anti-inflammatory mediators or a reduction in post-injury TNF alpha (TNFalpha) expression. Since the attenuation of inflammatory-associated entities has also been linked to mild hypothermia, an established neuroprotective paradigm, the effect of HA on post-injury body temperature was also studied. HA mice and normothermic (NT) counterparts were examined using a closed head injury model. Cytokines were measured within the ipsilateral cortex. Pre-injury protein levels of anti-inflammatory interleukins 10 and 4 (IL-10, IL-4) were quantified by enzyme-linked immunosorbent assays (ELISA). mRNA and protein levels of TNFalpha were quantified during the initial 2 h post-injury using semi-quantitative and real-time polymerase chain reaction (sqRT-PCR and qRT-PCR) or ELISA, respectively. Rectal temperatures were measured. HA induced augmented pre-injury IL-10 expression and a post-injury reduction in TNFalpha mRNA levels, as well as altered expression dynamics of TNFalpha protein. TNFalpha protein levels decreased relative to the sham state in HA mice only. HA mice displayed sustained post-injury hypothermia, namely significantly lower body temperature at 4 h post-injury. Given the evidence on the neuroprotective nature of hypothermia and anti-inflammatory cytokines, we suggest that these changes may contribute to HA-induced neuroprotection.
authors.affiliation: Department of Pharmacology, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Na'ama A
authors.initials: NA
authors.lastname: Shein
authors.forename: Hanny
authors.initials: H
authors.lastname: Doron
authors.forename: Michal
authors.initials: M
authors.lastname: Horowitz
authors.forename: Victoria
authors.initials: V
authors.lastname: Trembovler
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Alexandrovich
authors.forename: Esther
authors.initials: E
authors.lastname: Shohami
mesh_terms: D000064:Acclimatization / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000150:complications*; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D006358:Hot Temperature; D007035:Hypothermia / Q000209:etiology*; D008297:Male; D051379:Mice; D013997:Time Factors
chemical_list: D016207:Cytokines