Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in
Jaime Ramos-Cejudo1, María Gutiérrez-Fernández2, Laura Otero-Ortega1
1From the Department of Neurology and Stroke Center, Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autónoma University of Madrid, Madrid, Spain (J.R.-C., M.G.-F., L.O.-O., B.R.-F., B.F., M.T.V.-C., E.D.-T.); and Laboratory for Imaging and Spectroscopy by Magnetic Resonance (LISMAR), Institute of Biomedical Research Alberto Sols, CSIC-UAM, Madrid, Spain (T.N.H., S.C.).
Background And Purpose:
Translational research is beginning to reveal the importance of trophic factors as a therapy for cellular brain repair. The purpose of this study was to analyze whether brain-derived neurotrophic factor (BDNF) administration could mediate oligodendrogenesis and remyelination after white matter injury in subcortical stroke.
Methods:
Ischemia was induced in rats by injection of endothelin-1. At 24 hours, 0.4 μg/kg of BDNF or saline was intravenously administered to the treatment and control groups, respectively. Functional evaluation, MRI, and fiber tract integrity on tractography images were analyzed. Proliferation (KI-67) and white matter repair markers (A2B5, 2',3'-cyclic-nucleotide 3'-phosphodiesterase [CNPase], adenomatous polyposis coli [APC], platelet-derived growth factor receptor alpha [PDGFR-α], oligodendrocyte marker O4 [O4], oligodendrocyte transcription factor [Olig-2], and myelin basic protein [MBP]) were analyzed at 7 and 28 days.
Results:
The BDNF-treated animals showed less functional deficit at 28 days after treatment than the controls (P<0.05). Although T2-MRI did not show differences in lesion size at 7 and 28 days between groups, diffusion tensor imaging tractography analysis revealed significantly better tract connectivity at 28 days in the BDNF group than in the controls (P<0.05). Increased proliferation of oligodendrocyte progenitors was observed in treated animals at 7 days (P<0.05). Finally, the levels of white matter repair markers (A2B5, CNPase, and O4 at 7 days; Olig-2 and MBP at 28 days) were higher in the BDNF group than in the controls (P<0.05).
Conclusions:
BDNF administration exerted better functional outcome, oligodendrogenesis, remyelination, and fiber connectivity than controls in rats subjected to subcortical damage in ischemic stroke.
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