Ischemic Preconditioning Mediates Neuroprotection against Ischemia in Mouse Hippocampal CA1 Neurons by Inducing Autophagy.
The hippocampal CA1 region is sensitive to hypoxic and ischemic injury but can be protected by ischemic preconditioning (IPC). However, the mechanism through which IPC protects hippocampal CA1 neurons is still under investigation. Additionally, the role of autophagy in determining the fate of hippocampal neurons is unclear. Here, we examined whether IPC induced autophagy to alleviate hippocampal CA1 neuronal death in vitro and in vivo with oxygen glucose deprivation (OGD) and bilateral carotid artery occlusion (BCCAO) models. Survival of hippocampal neurons increased from 51.5% ± 6.3% in the non-IPC group (55 min of OGD) to 77.3% ± 7.9% in the IPC group (15 min of OGD, followed by 55 min of OGD 24 h later). The number of hippocampal CA1 layer neurons increased from 182 ± 26 cells/mm2 in the non-IPC group (20 min of BCCAO) to 278 ± 55 cells/mm2 in the IPC group (1 min × 3 BCCAO, followed by 20 min of BCCAO 24 h later). Akt phosphorylation and microtubule-associated protein light chain 3 (LC3)-II/LC3-I expression were increased in the preconditioning group. Moreover, the protective effects of IPC were abolished only by inhibiting the activity of autophagy, but not by blocking the activation of Akt in vitro. Using in vivo experiments, we found that LC3 expression was upregulated, accompanied by an increase in neuronal survival in hippocampal CA1 neurons in the preconditioning group. The neuroprotective effects of IPC on hippocampal CA1 neurons were completely inhibited by treatment with 3-MA. In contrast, hippocampal CA3 neurons did not show changes in autophagic activity or beneficial effects of IPC. These data suggested that IPC may attenuate ischemic injury in hippocampal CA1 neurons through induction of Akt-independent autophagy.
Department of Neurology, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin, China.
Chunlin
C
Gao
Department of Neuroscience, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin Neurosurgery Institute, Tianjin, China.
Ying
Y
Cai
Department of Pathology, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin, China.
Xuebin
X
Zhang
Department of Neuroscience, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin Neurosurgery Institute, Tianjin, China.
Huiling
H
Huang
Department of Neurology, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin, China.
Jin
J
Wang
Department of Neurology, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin, China.
Yajing
Y
Wang
Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin Neurosurgery Institute, Tianjin, China.
Xiaoguang
X
Tong
Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin Neurosurgery Institute, Tianjin, China.
Jinhuan
J
Wang
Department of Neurology, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin, China.
Jialing
J
Wu
D000818:Animals; D001343:Autophagy; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D002470:Cell Survival; D005260:Female; D019194:Ischemic Preconditioning; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology*; D011247:Pregnancy; D015427:Reperfusion Injury / Q000517:prevention & control*