Citation

Krieg SM, Voigt F, Knuefermann P, Kirschning CJ, Plesnila N, Ringel F. Front. Neurol. 2017; 8: e455.

Affiliation

Department of Neurosurgery, University of Mainz, Mainz, Germany.

Copyright

(Copyright © 2017, Frontiers Research Foundation)

DOI

10.3389/fneur.2017.00455

PMID

28912751

PMCID

PMC5582067

Abstract

Danger-associated molecular patterns are released by damaged cells and trigger neuroinflammation through activation of non-specific pattern recognition receptors, e.g., toll-like receptors (TLRs). Since the role of TLR2 and 4 after traumatic brain injury (TBI) is still unclear, we examined the outcome and the expression of pro-inflammatory mediators after experimental TBI in Tlr2/4(-/-) and wild-type (WT) mice. Tlr2/4(-/-) and WT mice were subjected to controlled cortical injury and contusion volume and brain edema formation were assessed 24 h thereafter. Expression of inflammatory markers in brain tissue was measured by quantitative PCR 15 min, 3 h, 6 h, 12 h, and 24 h after controlled cortical impact (CCI). Contusion volume was significantly attenuated in Tlr2/4(-/-) mice (29.7 ± 0.7 mm(3) as compared to 33.5 ± 0.8 mm(3) in WT; p < 0.05) after CCI while brain edema was not affected. Only interleukin (IL)-1β gene expression was increased after CCI in the Tlr2/4(-/-) relative to WT mice. Inducible nitric oxide synthetase, TNF, IL-6, and COX-2 were similar in injured WT and Tlr2/4(-/-) mice, while the increase in high-mobility group box 1 was attenuated at 6 h. TLR2 and 4 are consequently shown to potentially promote secondary brain injury after experimental CCI via neuroinflammation and may therefore represent a novel therapeutic target for the treatment of TBI.

Language: en

Keywords

brain edema; intracranial pressure; secondary brain damage; toll-like receptors; traumatic brain injury