Genetic regulation of microglia activation, complement expression, and neurodegeneration in a rat model of traumatic brain injury.
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.
Bellander
Bo-Michael
BM
Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska University Hospital Solna, R3.02, S-171 76, Stockholm, Sweden. bo-michael.bellander@karolinska.se
Lidman
Olle
O
Ohlsson
Marcus
M
Meijer
Britt
B
Piehl
Fredrik
F
Svensson
Mikael
M
D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D003165:Complement System Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D053331:Ectodysplasins / Q000378:metabolism; D005452:Fluoresceins; D005786:Gene Expression Regulation / Q000502:physiology*; D051917:Leukosialin / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism*; D009410:Nerve Degeneration / Q000209:etiology* / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism; D009930:Organic Chemicals; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000378:metabolism
D039481:CD11b Antigen; D053331:Ectodysplasins; D005452:Fluoresceins; D051917:Leukosialin; D009930:Organic Chemicals; D012333:RNA, Messenger; C435731:fluoro jade; D003165:Complement System Proteins