Low-frequency Stimulation at the Subiculum is Anti-convulsant and Anti-drug-resistant in a Mouse Model of Lamotrigine-resistant Temporal Lobe Epilepsy

摘要

Establishment of a mouse model of TLE with delayed-onset lamotrigine (LTG) resistance. A Schematic of the establishment of the LTG-resistant TLE model. Electrodes were implanted into the CA3 and subiculum of C57 mice, which were then divided into two groups, one receiving a sub-therapeutic dose of LTG and the other receiving vehicle along with kindling acquisition. B, C The progression of seizure stage (B) and afterdischarge duration (ADD) (C) showed no differences between vehicle and LTG groups. D, E LTG at a therapeutic dose had an anti-convulsant effect in the vehicle but not in the LTG group (n = 11 for vehicle, n = 18 for LTG). LTG treatment significantly lowered the seizure stage (D, ***P < 0.001, unpaired t test) and shortened the ADD (E, *P = 0.047, ***P < 0.001, unpaired t test) in kindled mice of the vehicle group compared with the LTG group. F Representative seizure EEGs under LTG treatment from the vehicle and LTG groups.