Cerebral Ischemic Preconditioning Aggravates Death of Oligodendrocytes

作者全名:"Guan, Teng; Guo, Ying; Li, Chengren; Zhou, Ting; Yu, Qiang; Yang, Chaoxian; Zhang, Guohui; Kong, Jiming"

作者地址:"[Guan, Teng; Guo, Ying; Zhou, Ting; Yu, Qiang; Kong, Jiming] Univ Manitoba, Dept Human Anat & Cell Sci, Winnipeg, MB R3E 0J9, Canada; [Guo, Ying; Zhang, Guohui] Hebei North Univ, Dept Forens Med, Zhangjiakou 075000, Peoples R China; [Li, Chengren] Guiqian Int Gen Hosp, Dept Obstet & Gynecol, Guiyang 550024, Peoples R China; [Zhou, Ting] Chongqing Med Univ, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Yang, Chaoxian] Southwest Med Univ, Sch Basic Med Sci, Dept Anat & Histoembryol, Luzhou 646099, Peoples R China"

通信作者:"Kong, JM (通讯作者),Univ Manitoba, Dept Human Anat & Cell Sci, Winnipeg, MB R3E 0J9, Canada."












关键词:neurodegeneration; preconditioning; white matter injury; ischemic stroke; oligodendrocytes

摘要:"Neurodegeneration can benefit from ischemic preconditioning, a natural adaptive reaction to sublethal noxious stimuli. Although there is growing interest in advancing preconditioning to preserve brain function, preconditioning is not yet considered readily achievable in clinical settings. One of the most challenging issues is that there is no fine line between preconditioning stimuli and lethal stimuli. Here, we show deleterious effect of preconditioning on oligodendrocyte precursor cells (OPCs). We identified Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3), a mitochondrial BH3-only protein specifically involved in OPCs loss after preconditioning. Repeated ischemia stabilized BNIP3 and increased the vulnerability of OPCs to subsequent ischemic events. BNIP3 became mitochondrial-bound and was concurrent with the dysfunction of monocarboxylate transporter 1 (MCT1). Inhibition of BNIP3 by RNAi or necrostatin-1 (Nec-1) and knocking out of BNIP3 almost completely prevented OPCs loss and preserved white matter integrity. Together, our results suggest that the unfavorable effect of BNIP3 on OPCs should be noted for safe development of ischemic tolerance. BNIP3 inhibition appears to be a complementary approach to improve the efficacy of preconditioning for ischemic stroke."

基金机构:ALS Canada; Brain Canada; By-Health China

基金资助正文:"This study was supported by grants from ALS Canada, Brain Canada, and By-Health China."