title: Increased oligodendrogenesis by humanin promotes axonal remyelination and neurological recovery in hypoxic/ischemic brains.
abstract: Oligodendrocytes are the predominant cell type in white matter and are highly vulnerable to ischemic injury. The role of oligodendrocyte dysfunction in ischemic brain injury is unknown. In this study, we used a 24-amino acid peptide S14G-Humanin (HNG) to examine oligodendrogenesis and neurological functional recovery in a hypoxic/ischemic (H/I) neonatal model. Intraperitoneal HNG pre-treatment decreased infarct volume following H/I injury. Delayed HNG treatment 24 h after H/I injury did not reduce infarct volume but did decrease neurological deficits and brain atrophy. Delayed HNG treatment did not attenuate axonal demyelination at 48 h after H/I injury. However, at 14 d after H/I injury, delayed HNG treatment increased axonal remyelination, the thickness of corpus callosum at the midline, the number of Olig2(+) /BrdU(+) cells, and levels of brain-derived neurotrophic factor (BDNF). Our results suggest that targeting oligodendrogenesis via delayed HNG treatment may represent a promising approach for the treatment of stroke.
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, the Second Affiliated Hospital of Soochow University, Soochow University, Suzhou City, China; The Institute of Neuroscience, Soochow University, Suzhou City, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Miao
authors.forename: Balvin H L
authors.initials: BH
authors.lastname: Chua
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Hamdy
authors.forename: Quan-Guang
authors.initials: QG
authors.lastname: Zhang
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Liu
authors.forename: Xingshun
authors.initials: X
authors.lastname: Xu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001284:Atrophy / Q000473:pathology; D001369:Axons / Q000187:drug effects / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D055495:Neurogenesis / Q000187:drug effects*; D009836:Oligodendroglia / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D047908:Intracellular Signaling Peptides and Proteins; C427211:humanin
keywords: brain-derived neurotrophic factor; humanin; hypoxic/ischemic injury; oligodendrocyte; remyelination