Toll‐like receptor (TLR)‐2 and TLR‐4 regulate inflammation, gliosis, and myelin sparing after spinal cord injury

Journal of Neurochemistry - Tập 102 Số 1 - Trang 37-50 - 2007
Kristina A. Kigerl1, Wenmin Lai2, Serge Rivest3, Ronald P. Hart4, Abhay R. Satoskar2, Phillip G. Popovich1
1Integrated Biomedical Science Graduate Program, College of Medicine, Ohio State University, Columbus, Ohio, USA.
2Department of Molecular Virology, Immunology & Medical Genetics, College of Medicine, Ohio State University, Columbus, Ohio, USA
3CHUL Research Center, Laval University, Québec, Canada.
4W. M. Keck Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey, USA

Tóm tắt

Abstract

Activation of macrophages via toll‐like receptors (TLRs) is important for inflammation and host defense against pathogens. Recent data suggest that non‐pathogenic molecules released by trauma also can trigger inflammation via TLR2 and TLR4. Here, we tested whether TLRs are regulated after sterile spinal cord injury (SCI) and examined their effects on functional and anatomical recovery. We show that mRNA for TLR1, 2, 4, 5, and 7 are increased after SCI as are molecules associated with TLR signaling (e.g. MyD88, NFκB). The significance of in vivo TLR2 and TLR4 signaling was evident in SCI TLR4 mutant (C3H/HeJ) and TLR2 knockout (TLR2−/−) mice. In C3H/HeJ mice, sustained locomotor deficits were observed relative to SCI wild‐type control mice and were associated with increased demyelination, astrogliosis, and macrophage activation. These changes were preceded by reduced intraspinal expression of interleukin‐1β mRNA. In TLR2−/− mice, locomotor recovery also was impaired relative to SCI wild‐type controls and novel patterns of myelin pathology existed within ventromedial white matter – an area important for overground locomotion. Together, these data suggest that in the absence of pathogens, TLR2 and TLR4 are important for coordinating post‐injury sequelae and perhaps in regulating inflammation and gliosis after SCI.

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Journal of Neurochemistry

Tập 102 Số 1

37-50

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