title: The role of autophagic and lysosomal pathways in ischemic brain injury.
abstract: Autophagy is involved in neural cell death after cerebral ischemia. Our previous studies showed that rapamycin-induced autophagy decreased the rate of apoptosis, but the rate of apoptosis was creased after the autophagy inhibitor, 3-methyladenine, was used. In this study, a suture-occluded method was performed to generate a rat model of brain ischemia. Under a transmission electron microscope, autophagic bodies and autophagy lysosomes were markedly accumulated in neurons at 4 hours post brain ischemic injury, with their numbers gradually reducing over time. Western blotting demonstrated that protein levels of light chain 3-II and cathepsin B were significantly increased within 4 hours of ischemic injury, but these levels were not persistently upregulated over time. Confocal microscopy showed that autophagy was mainly found in neurons with positive light chain 3 signal. Injection of rapamycin via tail vein promoted the occurrence of autophagy in rat brain tissue after cerebral ischemia and elevated light chain 3 and cathepsin B expression. However, injection of 3-methyladenine significantly diminished light chain 3-II and cathepsin B expression. Results verified that autophagic and lysosomal activity is increased in ischemic neurons. Abnormal components in cells can be eliminated through upregulating cell autophagy or inhibiting autophagy after ischemic brain injury, resulting in a dynamic balance of substances in cells. Moreover, drugs that interfere with autophagy may be potential therapies for the treatment of brain injury.
authors.affiliation: Department of Neurology, Shanghai Pudong New Area Zhoupu Hospital, Shanghai 234318, China.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Department of Neurology, the Sixth People's Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai 200233, China.
authors.forename: Yinyi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Neurology, Shanghai Pudong New Area Zhoupu Hospital, Shanghai 234318, China ; Department of Neurology, the Sixth People's Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai 200233, China.
authors.forename: Kangyong
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Suzhou University School of Medicine, Suzhou 215123, Jiangsu Province, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Neurology, the Sixth People's Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai 200233, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Neurology, the Sixth People's Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai 200233, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Neurology, the Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Neurology, the Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Shanghai Pudong New Area Zhoupu Hospital, Shanghai 234318, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Neurology, Shanghai Pudong New Area Zhoupu Hospital, Shanghai 234318, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Shi
authors.affiliation: Department of Neurology, Shanghai Pudong New Area Zhoupu Hospital, Shanghai 234318, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Shanghai Pudong New Area Zhoupu Hospital, Shanghai 234318, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Shanghai Pudong New Area Zhoupu Hospital, Shanghai 234318, China.
authors.forename: Meizhen
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Neurology, the Sixth People's Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai 200233, China.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Sun
keywords: autophagy; brain injury; cathepsin B; cerebral ischemia; grants-supported paper; light chain 3; lysosome; neural regeneration; neuron; neuroprotection; neuroregeneration