Brain-Derived Neurotrophic Factor Administration Mediated Oligodendrocyte Differentiation and Myelin Formation in Subcortical Ischemic Stroke. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Ramos-Cejudo, Jaime; Gutiérrez-Fernández, María; Otero-Ortega, Laura; Rodríguez-Frutos, Berta; Fuentes, Blanca; Vallejo-Cremades, Maria Teresa; Hernanz, Teresa Navarro; Cerdán, Sebastián; Díez-Tejedor, Exuperio
• Is Part Of: Stroke. Volume 46:Issue 1(2015)
• Publication Date: 2015-01
• Subjects: Cerebrovascular disease -- Periodicals; Cerebral circulation -- Periodicals; 616.81
• DOI: 10.1161/STROKEAHA.114.006692
• Languages: English
• ISSNs: 0039-2499

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background and Purpose—</title> <p>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.</p> </sec> <sec> <title>Methods—</title> <p>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.</p> </sec> <sec> <title>Results—</title> <p>The BDNF-treated animals showed less functional deficit at 28 days after treatment than the controls (<italic>P</italic><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 (<italic>P</italic><0.05). Increased proliferation of oligodendrocyte progenitors was observed in treated animals at 7 days (<italic>P</italic><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 (<italic>P</italic><0.05).</p> </sec> <sec> <title>Conclusions—</title> <p>BDNF administration exerted better functional outcome, oligodendrogenesis, remyelination, and fiber connectivity than controls in rats subjected to subcortical damage in ischemic stroke.</p> </sec> </abstract>