title: 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.
authors.affiliation: Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Lee
authors.forename: Karen L
authors.initials: KL
authors.lastname: Neitzel
authors.forename: Annalise
authors.initials: A
authors.lastname: Di Marco
authors.forename: Ralph
authors.initials: R
authors.lastname: Laufer
authors.forename: A John
authors.initials: AJ
authors.lastname: MacLennan
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism*; D020934:Ciliary Neurotrophic Factor / Q000031:analogs & derivatives* / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006131:Growth Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D007150:Immunohistochemistry / Q000379:methods; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020801:Receptor, Ciliary Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D050796:STAT3 Transcription Factor; D013238:Stereotaxic Techniques; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014278:Trigeminal Nuclei / Q000166:cytology / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism
chemical_list: D020934:Ciliary Neurotrophic Factor; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D020801:Receptor, Ciliary Neurotrophic Factor; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; C500726:ciliary neurotrophic factor, Ala(152)-Ala(155)-Asp(166)-His(167)-