Neurosteroids reduce inflammation after TBI through CD55 induction.
The inflammatory cascade that follows traumatic brain injury may lead to secondary cell death and can impede recovery of function. Complement factors and their convertases are increased in glia after brain injury and lead to the production of inflammatory products that kill vulnerable neurons. Progesterone and its metabolite allopregnanolone (5alpha-pregnan-3beta-ol-20-one) have been shown to reduce the expression of inflammatory cytokines in the acute stages of brain injury, although how they do this is not completely understood. In this study we show that both progesterone and allopregnanolone treatments enhance the production of CD55 following contusion injuries of the cerebral cortex in rats. CD55, a single-chain type 1 cell surface protein, is a potent inhibitor of the complement convertases which are activators of the inflammatory cascade. The increased expression of CD55 could be an important mechanism by which steroids help to reduce the cerebral damage caused by inflammation.
VanLandingham
Jacob W
JW
Department of Emergency Medicine, Emory University, Atlanta, GA, USA.
Cekic
Milos
M
Cutler
Sarah
S
Hoffman
Stuart W
SW
Stein
Donald G
DG
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001930:Brain Injuries / Q000150:complications* / Q000503:physiopathology; D018958:CD55 Antigens / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology; D050577:Complement C3-C5 Convertases / Q000187:drug effects / Q000378:metabolism; D003165:Complement System Proteins / Q000096:biosynthesis / Q000276:immunology; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D005911:Gliosis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D011280:Pregnanolone / Q000494:pharmacology / Q000627:therapeutic use; D011374:Progesterone / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013256:Steroids / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome