Brain-Derived Neurotrophic Factor Administration Mediated Oligodendrocyte Differentiation and Myelin Formation in Subcortical Ischemic Stroke

作者：Ramos Cejudo Jaime; Gutierrez Fernandez Maria; Otero Ortega Laura; Rodriguez Frutos Berta; Fuentes Blanca; Teresa Vallejo Cremades Maria; Navarro Hernanz Teresa; Cerdan Sebastian; Diez Tejedor Exuperio^*

来源：Stroke, 2015, 46(1): 221-+.

DOI：10.1161/STROKEAHA.114.006692

• brain-derived neurotrophic factor
• endothelin-1
• subcortical stroke

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 mu g/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-a], 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.

• 出版日期2015-1