ABSTRACT
Objective
Peri-infarct depolarizations (PIDs) are spontaneous waves that propagate slowly across the penumbra region following stroke, contributing to secondary infarct growth and negatively affecting stroke outcomes. KATP channels are generally spread in the brain. Under conditions of ischemia and/or hypoxia, KATP channels play a cytoprotective role in neurons. However, it is still unknown whether KATP channels are involved in the initiation and propagation of PIDs.
Methods
The Kir6.1 knockout (Kir6.1−/−) mice, Kir6.2 knockout (Kir6.2−/−) mice, and wild-type C57Bl6 mice (n = 8) were used. The middle cerebral artery occlusion (MCAO) stroke model was made and PIDs were detected by an optical intrinsic signal (OIS) imaging system.
Results
Much more PIDs appeared in Kir6.1−/−mice than that in Kir6.2−/− and WT mice in both the first hour and 4 hours following MCAO (3.9 ± 0.7 vs. 1.5 ± 0.3, p < 0,05; 3.9 ± 0.7 vs. 1.9 ± 0.3, p < 0.05; 20.0 ± 2.5 vs. 10.4 ± 2.4, p < 0.05; 20.0 ± 2.5 vs. 11.3 ± 1.4, p < 0.05). Furthermore, the first PID occurred much earlier in Kir6.1−/− mice than that in Kir6.2−/− mice and WT mice (21.3 ± 2.1 min vs. 34.1 ± 4.8 min, p < 0.05; 21.3 ± 2.1 min vs. 38.8 ± 3.4 min, p < 0.01). No significant differences in other characteristics of PIDs including originating sites, duration time, propagation patterns, and velocity were detected. Additionally, the migration of originating sites was observed.
Conclusion
This study shows that loss of Kir6.1, not Kir6.2 facilitates the induction of PIDs in focal cerebral ischemia, indicating that Kir6.1-forming channels in the brain may provide protection against PIDs.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Author’s contributions
ZLZ and JPL designed these experiments, analyzed the data, and wrote the manuscript. ZLZ and ZYL performed the experiments.
Additional information
Funding
Notes on contributors
Zelong Zheng
Zelong Zheng is currently an attending physician in the Department of Neurosurgery of Guangzhou First People’s Hospital, School of Medicine, South China University of Technology. He completed his Doctoral research in the field of spreading depolarization at Heidelberg University. His research mainly focuses on the role of spreading depolarization in brain injury. In his record, he holds many international publications in the field of neuroscience.
Zhenyu Li
Zhenyu Li is currently a resident in the Department of Neurosurgery of Guangzhou First People’s Hospital, School of Medicine, South China University of Technology. He got a Master’s degree from Southern Medical University. During his Master’s at the Department of Neurosurgery, he executed his project in the field of neuroscience in particular on Alzheimer’s Disease.
Jianping Lv
Jianping Lv is the Deputy Director of the Department of Neurosurgery of Guangzhou First People’s Hospital, School of Medicine, South China University of Technology. He completed his Ph.D. at Sun Yat-Sen University. His research focuses on spreading depolarization and cerebrovascular diseases. And he has got many international publications.