Citation

Truettner J, Bramlett HM, Dietrich WD. J. Neurotrauma 2018; ePub(ePub): ePub.

Affiliation

University of Miami, Neurological Surgery , 1095 NW 14 Ter (R48) , Miami, Florida, United States , 33136 ; ddietrich@miami.edu.

Copyright

(Copyright © 2018, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2017.5303

PMID

29108477

Abstract

Mild traumatic brain injury (mTBI) or concussion represents the majority of TBIs brain trauma in the United States. The pathophysiology of mTBI is complex and may include both focal and diffuse injury patterns. In addition to altered circuit dysfunction and diffuse traumatic axonal injury (DTAI), chronic neuroinflammation has also been implicated in the pathophysiology of mTBI. Recently, our laboratory has reported the detrimental effects of mild hyperthermic mTBI in terms of worsening histopathological and behavioral outcomes. To clarify the role of temperature-sensitive neuroinflammatory processes on these consequences, we evaluated the effects of elevated brain temperature (39°C) on altered microglia/macrophage phenotype patterns after mTBI, changes in leukocyte recruitment and TDAI. Sprague Dawley male rats underwent mild parasaggital fluid-percussion injury under normothermic (37°C) or hyperthermic (39°C) conditions. Cortical and hippocampal regions were analyzed using several cellular and molecular outcome measures. At 24 hrs, the ratio of iNOS positive (M1 type phenotype) to arginase positive (M2 type phenotype) cells after hyperthermic mTBI showed an increase compared to normothermia by flow cytometry. Inflammatory response gene arrays also demonstrated a significant increase in several classes of pro-inflammatory genes with hyperthermia treatment over normothermia. The injury-induced expression of Ccl2 and alpha-2-macroglobulin were also increased with hyperthermic mTBI. With western blot analysis, an increase in CD18 and ICAM-1 with hyperthermia and a significant increase in Iba1 reactive microglia are reported in the cerebral cortex. Together, these results demonstrate significant differences in the cellular and molecular consequences of raised brain temperature at the time of mTBI. The observed polarization towards a M1-phenotype with mild hyperthermia would be expected to contribute toaugment chronic inflammatory cascades, sustained functional deficits, and increased vulnerability to secondary insults. Mild elevations in brain temperature may contribute to the more severe and longer lasting consequence of mTBI or concussion commonly reported in some patients.

Language: en

Keywords

BLOOD-BRAIN BARRIER DYSFUNCTION; INFLAMMATION; TRAUMATIC BRAIN INJURY