Spatiotemporal pattern of neuroinflammation after impact-acceleration closed head injury in the rat.
Inflammatory processes have been implicated in the pathogenesis of traumatic brain damage. We analyzed the spatiotemporal expression pattern of the proinflammatory key molecules: interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and inducible nitric oxide synthase in a rat closed head injury (CHI) paradigm. 51 rats were used for RT-PCR analysis after CHI, and 18 for immunocytochemistry. We found an early upregulation of IL-1beta, IL-6, and TNF-alpha mRNA between 1h and 7h after injury; the expression of iNOS mRNA only revealed a significant increase at 4h. After 24h, the expression decreased towards baseline levels, and remained low until 7d after injury. Immunocytochemically, IL-1beta induction was localized to ramified microglia in areas surrounding the primary impact place as well as deeper brain structures. Our study shows rapid induction of inflammatory gene expression that exceeds by far the primary impact site and might therefore contribute to tissue damage at remote sites.
Rooker
Servan
S
Department of Neurosurgery, Univeristy Hospital Antwerp, Edegem, Belgium.
Jander
Sebastian
S
Van Reempts
Jos
J
Stoll
Guido
G
Jorens
Philippe G
PG
Borgers
Marcel
M
Verlooy
Jan
J
D000818:Animals; D001921:Brain / Q000473:pathology; D016489:Head Injuries, Closed / Q000175:diagnosis* / Q000473:pathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000175:diagnosis* / Q000473:pathology*; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II