title: Transferring Xenogenic Mitochondria Provides Neural Protection Against Ischemic Stress in Ischemic Rat Brains.
abstract: Transferring exogenous mitochondria has therapeutic effects on damaged heart, liver, and lung tissues. Whether this protective effect requires the symbiosis of exogenous mitochondria in host cells remains unknown. Here xenogenic mitochondria derived from a hamster cell line were applied to ischemic rat brains and rat primary cortical neurons. Isolated hamster mitochondria, either through local intracerebral or systemic intra-arterial injection, significantly restored the motor performance of brain-ischemic rats. The brain infarct area and neuronal cell death were both attenuated by the exogenous mitochondria. Although internalized mitochondria could be observed in neurons and astrocytes, the low efficacy of mitochondrial internalization could not completely account for the high rate of rescue of the treated neural cells. We further illustrated that disrupting electron transport or ATPase synthase in mitochondria significantly attenuated the protective effect, suggesting that intact respiratory activity is essential for the mitochondrial potency on neural protection. These results emphasize that nonsymbiotic extracellular mitochondria can provide an effective cell defense against acute injurious ischemic stress in the central nervous system.
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Po-Jui
authors.initials: PJ
authors.lastname: Huang
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Kuo
authors.forename: Hsiu-Chin
authors.initials: HC
authors.lastname: Lee
authors.forename: Ching-I
authors.initials: CI
authors.lastname: Shen
authors.forename: Fu-Chou
authors.initials: FC
authors.lastname: Cheng
authors.forename: Shih-Fang
authors.initials: SF
authors.lastname: Wu
authors.forename: Jui-Chih
authors.initials: JC
authors.lastname: Chang
authors.forename: Hung-Chuan
authors.initials: HC
authors.lastname: Pan
authors.forename: Shinn-Zong
authors.initials: SZ
authors.lastname: Lin
authors.forename: Chin-San
authors.initials: CS
authors.lastname: Liu
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Su
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology / Q000628:therapy*; D016923:Cell Death / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival; D006224:Cricetinae; D004579:Electron Transport / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000628:therapy*; D007269:Injections, Intra-Arterial; D008297:Male; D008928:Mitochondria / Q000637:transplantation*; D009474:Neurons / Q000166:cytology; D000066829:Neuroprotection / Q000502:physiology*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous
chemical_list: D018696:Neuroprotective Agents