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Genetic regulation of microglia activation, complement expression, and neurodegeneration in a rat model of traumatic brain injury

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Abstract

Secondary brain damage following traumatic brain injury in part depends on neuroinflammation, a process where genetic factors may play an important role. We examined the response to a standardized cortical contusion in two different inbred rat strains, Dark Agouti (DA) and Piebald Virol Glaxo (PVG). Both are well characterized in models of autoimmune neuroinflammation, where DA is susceptible and PVG resistant. We found that infiltration of polymorphonuclear granulocytes (PMN) at 3-day postinjury was more pronounced in PVG. DA was more infiltrated by T cells at 3-day postinjury, showed an enhanced glial activation at 7-day postinjury and higher expression of C3 complement at 7-day postinjury. Neurodegeneration, assessed by Fluoro-Jade, was also more pronounced in the DA strain at 30-day postinjury. These results demonstrate differences in the response to cortical contusion injury attributable to genetic influences and suggest a link between injury-induced inflammation and neurodegeneration. Genetic factors that regulate inflammation elicited by brain trauma may be important for the development of secondary brain damage.

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Abbreviations

cDNA:

Complementary DNA

CNS:

Central nervous system

DA:

Dark Agouti

DAB:

3,3′-diaminobenzidine

DDT:

Dithiothreitol

dH2O:

Distilled water

DNA:

Deoxyribonucleic acid

EAE:

Experimental allergic encephalitis

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GFAP:

Glial fibrillary acidic protein

IR:

Immunoreactivity

MAC:

Membrane attack complex

MHC:

Major Histocompatibility Complex

mRNA:

Messenger RNA

PBS:

Phosphate Buffer solution

PCR:

Polymerase chain reaction

PMN:

Polymorphonuclear granulocytes

PVG :

Piebald Virol Glaxo

RNA:

Ribonucleic acid

ROI:

Region of interest

RT-PCR:

Reverse transcriptase-polymerase chain reaction

TBI:

Traumatic brain injury

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Acknowledgments

This work is supported by 6th Framework Program of the European Union; NeuroproMiSe, LSHM-CT-2005-018637 and the EURATools, LSHG-CT-2005-019015; as well as by grants from the Wadsworth Foundation, Torsten and Ragnar Söderberg’s Foundation, Björklund’s Foundation, Nils and Bibbi Jenssen’s Foundation, Montel Williams Foundation, Magn.

Bergvall’s Foundation, the Swedish Society for Medical Research, the Swedish Research Council, and the Swedish Association of Persons with Neurologically Disabilities.

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Authors and Affiliations

  1. Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska University Hospital Solna, R3.02, S-171 76, Stockholm, Sweden

    Bo-Michael Bellander, Marcus Ohlsson, Britt Meijer & Mikael Svensson

  2. Department of Clinical Neuroscience, Section for Clinical CNS Research, Karolinska University Hospital Solna, S-171 76, Stockholm, Sweden

    Olle Lidman & Fredrik Piehl

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  1. Bo-Michael Bellander
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  2. Olle Lidman
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  3. Marcus Ohlsson
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Correspondence to Bo-Michael Bellander.

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Bellander, BM., Lidman, O., Ohlsson, M. et al. Genetic regulation of microglia activation, complement expression, and neurodegeneration in a rat model of traumatic brain injury. Exp Brain Res 205, 103–114 (2010). https://doi.org/10.1007/s00221-010-2342-z

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