Experimental diffuse axonal injury induces enhanced neuronal C5a receptor mRNA expression in rats.
Several studies suggest the involvement of the complement system in the pathophysiology of traumatic brain injury (TBI). Since the intrathecal generation of anaphylatoxin C5a has been shown to mediate inflammatory effects within the central nervous system, we sought to characterize the cellular expression of the mRNA for the C5a receptor (C5aR, CD88) in brains of rats with experimental diffuse axonal injury (DAI) by in situ hybridization. Infiltrating leukocytes expressing C5aR mRNA were seen in meninges and lateral ventricles as early as 4 h after induction of DAI. The number of infiltrating C5aR-positive cells increased gradually up to 24 h after trauma. Within the brain parenchyma, up-regulation of C5aR mRNA expression was first seen in cerebellar Purkinje cells within 8 h. At 24 h after TBI, expression of C5aR mRNA was widespread bilaterally throughout the cortex and cerebellum, the cellular expression being restricted to pyramidal neurons and Purkinje cells. The intensity of C5aR transcript signals on neurons increased further up to 96 h after trauma. Ligand binding of C5a to its receptor on neurons might mediate previously unknown functions, thus possibly leading to neurotoxicity and secondary neuronal damage after TBI.
Stahel
P F
PF
Department of Microbiology, University of Alabama at Birmingham, 35294, USA.
Kossmann
T
T
Morganti-Kossmann
M C
MC
Hans
V H
VH
Barnum
S R
SR
D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002552:Cerebral Ventricles / Q000378:metabolism; D015936:Complement C5a; D017403:In Situ Hybridization; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008578:Meninges / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000235:genetics*
D015703:Antigens, CD; D012333:RNA, Messenger; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D015936:Complement C5a