Authors :
Ru Liu, PhD – Beijing Tiantan Hospital, Capital Medical University; Lei Sun, PHD – Department of Neurology, – Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan, China.; Le Du, MS – School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, China.; Ci Li, MS – School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, China.; Zahra Aqeela, PhD – School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, China.; Xi Guo, MS – Beijing Tiantan Hospital, Capital Medical University; Meng Jia, PhD – Beijing Tiantan Hospital, Capital Medical University; Tingting Yu, PhD – Beijing Tiantan Hospital, Capital Medical University; Qian Zhang, PhD – Beijing Tiantan Hospital, Capital Medical University; Qun Wang, MD, PhD – Beijing Tiantan Hospital, Capital Medical University; Jianping Wu, PhD – Beijing Tiantan Hospital, Capital Medical University
This is a Late Breaking abstractRationale: Mutations of the sodium-activated potassium channel K
Na1.1, has been reported in multiple epileptic disorders. However, whether K
Na1.1 channel is involved in epileptogenesis after traumatic brain injury (TBI) remains unknown.
Methods: Firstly, we used EEG and patch-clamp recordings to examine spontaneous seizure activity, seizure susceptibility and neuronal excitability after TBI. Meanwhile, we explored the changes of K
Na1.1 channel following TBI. To further determine the role of K
Na1.1 channel after TBI, we built TBI models using the null mutant kcnt1
−/− mice and compared seizure activity with those on wild-type (WT) mice. Finally, we investigated whether the K
Na1.1 channel was regulated by the activated MAPK pathway after TBI in in vitro experiment.
Results: We found enhanced seizure susceptibility and increased neuronal excitability in the moderate TBI model. In addition, increased neuronal expression of K
Na1.1 channel around the lesion was also observed following TBI. Compared to WT littermates, kcnt1
−/− mice displayed decreased seizure susceptibility to the pentylenetetrazole (PTZ) after TBI. Moreover, we found that the p38 MAPK pathway after TBI upregulated the K
Na1.1 channel.
Conclusions: Taken together,
this study suggests that enhanced K
Na1.1 activated by inflammatory response contributes to seizure susceptibility in the moderate TBI model and provides a potential therapeutic target on the post-traumatic epilepsy.
Funding: This work was supported by the National Natural Science Foundation of China (81870935, J.W.), the startup fund from Capital Medical University Advanced Innovation Center for Human Brain Protection (20181101, J.W.), and the Natural Science Foundation of Beijing (7214224, M.J.).