Chronically increased ciliary neurotrophic factor and fibroblast growth factor-2 expression after spinal contusion in rats.
Demyelination and oligodendrocyte loss following spinal cord injury (SCI) are well documented. Recently, we showed oligodendrocyte progenitor cell (OPC) accumulation and robust oligodendrocyte genesis occurring along SCI lesion borders. We have since begun investigating potential mechanisms for this endogenous repair response. Here, we examined ciliary neurotrophic factor (CNTF) and fibroblast growth factor-2 (FGF-2) expression, because both factors alter progenitor proliferation and differentiation and are increased in several CNS disorders. We hypothesized that CNTF and FGF-2 would increase after SCI, especially in regions of enhanced oligogenesis. First, CNTF protein was quantified using Western blots, which revealed that CNTF protein continually rose through 28 days post injury (dpi). Next, by using immunohistochemistry, we examined the spatiotemporal expression of CNTF in cross-sections spanning the injury site. CNTF immunoreactivity was observed on astrocytes and oligodendrocytes in naïve and contused spinal cords. Significantly increased CNTF was detected in spared white and gray matter between 5 and 28 dpi compared with uninjured controls. By 28 dpi, CNTF expression was significantly higher along lesion borders compared with outlying spared tissue; a similar distribution of phosphorylated STAT3, a transcription factor up-regulated by CNTF and to a lesser extent FGF-2, was also detected. Because CNTF can potentiate FGF-2 expression, we examined the distribution of FGF-2+ cells. Significantly more FGF-2+ cells were noted along lesion borders at 7 and 28 dpi. Thus, both CNTF and FGF-2 are present in regions of elevated OPC proliferation and oligodendrocyte generation after SCI and therefore may play a role in injury-induced gliogenesis.
Tripathi
Richa B
RB
Neuroscience Graduate Studies Program and Department of Neuroscience, Center for Brain and Spinal Cord Repair, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
McTigue
Dana M
DM
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism*; D003288:Contusions / Q000378:metabolism* / Q000473:pathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D009416:Nerve Regeneration / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020801:Receptor, Ciliary Neurotrophic Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D015415:Biomarkers; D020934:Ciliary Neurotrophic Factor; D020801:Receptor, Ciliary Neurotrophic Factor; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D016222:Fibroblast Growth Factor 2