EXPERIMENTAL DIFFUSE AXONAL INJURY INDUCES ENHANCED NEURONAL C5A RECEPTOR MESSENGER-RNA EXPRESSION IN RATS

Several studies suggest the involvement of the complement system in th e pathophysiology of traumatic brain injury (TBI). Since the intrathec al generation of anaphylatoxin C5a has been shown to mediate inflammat ory effects within the central nervous system, we sought to characteri ze the cellular expression of the mRNA for the C5a receptor (C5aR, CD8 8) in brains of rats with experimental diffuse axonal injury (DAI) by in situ hybridization. Infiltrating leukocytes expressing C5aR mRNA we re seen in meninges and lateral ventricles as early as 4 h after induc tion of DAI. The number of infiltrating C5aR-positive cells increased gradually up to 24 h after trauma. Within the brain parenchyma, up-reg ulation of C5aR mRNA expression was first seen in cerebellar Purkinje cells within 8 h. At 24 h after TBI, expression of C5aR mRNA was wides pread bilaterally throughout the cortex and cerebellum, the cellular e xpression being restricted to pyramidal neurons and Purkinje cells. Th e intensity of C5aR transcript signals on neurons increased further up to 96 h after trauma. Ligand binding of C5a to its receptor on neuron s might mediate previously unknown functions, thus possibly leading to neurotoxicity and secondary neuronal damage after TBI. (C) 1997 Elsev ier Science B.V.