Penetrating brain injury leads to activation of ciliary neurotrophic factor receptors

Abstract

Endogenous injury response mechanisms likely reduce secondary neuronal loss following CNS trauma by activating growth factor receptors. Therefore, it is important to determine which growth factor receptors are activated in vivo by CNS trauma and which signal transduction pathways are affected in which cell types. We present a model of penetrating brain injury utilizing stereotaxic insertion of a fine needle. This procedure can be used to anatomically characterize injury response mechanisms through immediate, local application of pharmacological agents. We find, through immunohistochemistry, that injury of the rat facial motor nucleus leads to activation of STAT3, a neuronal survival factor, in the dendrites, nuclei and cytoplasm of the motor neurons. A similar response was observed with the trigeminal motor nucleus. Use of the ciliary neurotrophic factor (CNTF) receptor antagonist, AADH-CNTF, indicated that the STAT3 activation resulted largely, and perhaps entirely, from injury-induced activation of CNTF receptors.