期刊
JOURNAL OF THE NEUROLOGICAL SCIENCES
卷 357, 期 1-2, 页码 41-49出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jns.2015.06.062
关键词
Traumatic brain injury; Neurotrauma; Neuroinflammation; Pro- and anti-inflammatory cytokines; Secondary injury cascades; M1 and M2 responses
资金
- Kentucky Spinal Cord Head Injury Research Trust [12-16A]
Traumatic brain injury (TBI) elicits complex inflammatory assets (M1 and M2 responses) in the brain that include the expression of various cytokines/chemokines and the recruitment of blood cells, contributing secondary injury cascades (SIC), and also recovery processes. The modulation of such inflammatory assets might be a therapeutic option following TBI. The present study assesses a temporal profile of various molecular markers of M1 and M2 response in the hippocampus after TBI. Following a unilateral controlled cortical impact (CCI) on young rats, hippocampal tissues of each brain were harvested at 2, 4, 6, 10, and 24 h post trauma. Including shams (craniotomy only), half of the rats were assessed for gene expression and half for the protein of various markers for M1 [interferon-gamma (IFN gamma), tumor necrosis factor-alpha (TNF alpha), interleukin (1L)-1-beta (IL-1 beta), and IL-6] and M2 [IL-4, IL-10, IL-13, arginase 1 (Arg1), YM1, FIZZ1, and mannose receptor C-1 (MRC1)] responses. Analysis revealed that molecular markers of M1 and M2 responses have heterogeneous injury effects in the hippocampus and that time-post-injury is an important factor in determining inflammation status. With the heterogeneous gene expression of pro-inflammatory cytokines, M1 response was significantly elevated at 2 hand declined at 24 h after TBI, however, their levels remained higher than the sham rats. Except IFN gamma, proteins of M1 cytokines were significantly elevated in the first 24 h, and peaked between 2-6 h [TNF alpha (2 h), IL-1 beta (6 h), and IL-6 (4-6 h)]. With the heterogeneous relative gene expression of Arg1, YM1, FIZZ1, and MRC1,levels of M2 cytokines were peaked at 24 h post TBI. IL-10 and IL-13 expression appeared biphasic in the first 24 h. Protein values of IL-4 and IL-13 peaked at 24 h and IL-10 at 6 h post injury. Results suggest that the M1 response rises rapidly after injury and overpowers the initial, comparatively smaller, or transient M2 response. A treatment that can modulate inflammation, reduce SIC, and improve recovery should be initiated early (within 10 h) after TBI. (C) 2015 Published by Elsevier B.V.
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