Epilepsy research · 2026
Inflammation-mediated function enhancement of KNa channels promotes network hyperactivity in the peripheral cortex following TBI.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Sun Lei, Liu Ru, Han Xiong, Wang Na, Zhao Ting, Chen Yanan, Wu Jianping, Chen Junfan, Wang Qun
Аннотация
BACKGROUND: Post-traumatic epilepsy (PTE) is a common complication of traumatic brain injury (TBI). Studies have indicated that functional abnormalities of the sodium-activated potassium (KNa) channels are closely related to infantile "refractory epilepsy". However, whether and how the KNa channels are involved in the occurrence of PTE remains unknown.
METHODS: We used adult male C57BL/6 J mice to establish a controlled cortical impact (CCI) mice model with different severity levels. We implanted intracranial electrodes 7 days after injury to observe the spontaneous seizures in the moderately injured mice.vEEG was continuously recorded for 7 days (24 h/day). Then, a multi - electrode array (MEA) was performed 14 days after TBI to evaluate the network activity in the peripheral cortex of TBI lesions.Seven days after injury, we detected the expression of KNa channels around the injury site and the activation of glial cells through immunofluorescence staining. Finally, primary neuron cultures were used to verify whether or not the inflammatory factor upregulated KNa channels and affected neuronal excitability by activating the NF-κB pathway.
RESULTS: Through continuous vEEG monitoring, we observed abnormal electrographic discharges in the moderate TBI group (9 %, 2/22). MEA recording confirmed hyperactive network around the lesion, supporting that peripheral cortex may be the potential epileptogenic focus. Our findings revealed that expression of KNa channels was elevated in neuronal membranes in the peripheral cortex. Reactive astrocytes and activated microglia were observed in the injured ipsilateral cortex of the moderate and severe TBI mice. In primary neurons, we found that KNa currents were markedly increased after TNF-α stimulation. When the NF-κB signaling pathway was inhibited by SN50, the KNa currents were correspondingly decreased.
CONCLUSIONS: Our results suggest that network hyperactivity in the perilesional neocortex may be the origin of abnormal epileptiform discharge. Activation of glial cells around the lesion releases inflammatory factors that initiate the NF-κB signaling pathway and modulate the KNa channels, which may be a potential mechanism for the occurrence of PTE. This research had important implications for clarifying the origin of epileptic foci of TBI and identifying immune-based biomarkers to improve the prognosis of PTE.
METHODS: We used adult male C57BL/6 J mice to establish a controlled cortical impact (CCI) mice model with different severity levels. We implanted intracranial electrodes 7 days after injury to observe the spontaneous seizures in the moderately injured mice.vEEG was continuously recorded for 7 days (24 h/day). Then, a multi - electrode array (MEA) was performed 14 days after TBI to evaluate the network activity in the peripheral cortex of TBI lesions.Seven days after injury, we detected the expression of KNa channels around the injury site and the activation of glial cells through immunofluorescence staining. Finally, primary neuron cultures were used to verify whether or not the inflammatory factor upregulated KNa channels and affected neuronal excitability by activating the NF-κB pathway.
RESULTS: Through continuous vEEG monitoring, we observed abnormal electrographic discharges in the moderate TBI group (9 %, 2/22). MEA recording confirmed hyperactive network around the lesion, supporting that peripheral cortex may be the potential epileptogenic focus. Our findings revealed that expression of KNa channels was elevated in neuronal membranes in the peripheral cortex. Reactive astrocytes and activated microglia were observed in the injured ipsilateral cortex of the moderate and severe TBI mice. In primary neurons, we found that KNa currents were markedly increased after TNF-α stimulation. When the NF-κB signaling pathway was inhibited by SN50, the KNa currents were correspondingly decreased.
CONCLUSIONS: Our results suggest that network hyperactivity in the perilesional neocortex may be the origin of abnormal epileptiform discharge. Activation of glial cells around the lesion releases inflammatory factors that initiate the NF-κB signaling pathway and modulate the KNa channels, which may be a potential mechanism for the occurrence of PTE. This research had important implications for clarifying the origin of epileptic foci of TBI and identifying immune-based biomarkers to improve the prognosis of PTE.