Low-Frequency Stimulation at the Subiculum Prevents Extensive Secondary Epileptogenesis in Temporal Lobe Epilepsy
In the field of neuroscience, epilepsy has always been a disease of great concern, with significant challenges remaining in clinical research and treatment. Among these, the issue of secondary epileptogenesis has had a profound impact on academia and clinical treatment. Secondary epileptogenesis refers to the continuous spread of epileptic activity originating from a specific brain region (called the primary focus) to other brain regions, causing these areas to also develop the potential for epileptic activity. Studying the mechanisms of secondary epileptogenesis and its treatment methods is of great significance for improving the effectiveness of epilepsy treatment and reducing drug resistance.
The research team, composed of scholars from multiple renowned domestic and international research institutions including Shanghai Jiao Tong University, published their latest research findings in the “Neuroscience Bulletin,” proposing that low-frequency stimulation (LFS) applied to the subiculum can effectively prevent secondary epileptogenesis in temporal lobe epilepsy (TLE). The article was received on May 31, 2023, accepted on November 5, 2023, and published online on January 20, 2024. This study not only demonstrates the potential of LFS in preventing secondary epileptogenesis but, more importantly, points out that the subiculum can be a potential therapeutic target.
In the study, the research team used a mouse model to simulate TLE and set up two secondary foci: the contralateral CA3 region and the ipsilateral entorhinal cortex (EC). The researchers first performed primary kindling in the right CA3 region to simulate primary epileptogenesis, followed by kindling stimulation at the two designated secondary foci. The research data showed that compared to control mice without primary kindling, mice that underwent primary kindling displayed higher seizure sensitivity and accelerated kindling processes at the secondary foci. This suggests that primary kindling in the CA3 region can induce secondary epileptogenesis in the contralateral CA3 and ipsilateral EC.
The next key finding was that applying LFS to the ipsilateral subiculum immediately during primary kindling of the right CA3 could effectively prevent seizures at the secondary foci CA3 and EC. Importantly, the effect of LFS was related not only to its inhibitory action at the secondary foci but also to its interference with the enhancement of synaptic connections between the primary and secondary foci, providing a theoretical basis for LFS prevention of secondary epileptogenesis in TLE.
Further research in bioelectrophysiology confirmed that LFS can reduce the excitability of neurons in secondary foci by interfering with the enhancement of synaptic connections from the primary lesion to secondary foci. Data showed that LFS could significantly reduce the firing rate of glutamatergic neurons in secondary foci.
Overall, this study indicates that applying LFS to the subiculum can effectively prevent secondary epileptogenesis in TLE, and identifies the subiculum as a potentially important translational target. Its scientific value lies in providing a new perspective for understanding and treating secondary epileptogenesis, while its application value is reflected in potentially offering a new treatment strategy for clinical use.
The highlights of the study include discovering the unique preventive effect of subicular LFS on inhibiting secondary kindling, and subsequent experiments revealing that this effect is associated with both the direct anti-epileptic action of LFS and its impact on synaptic connections. These findings may contribute to the development of more effective epilepsy treatments.
The scientific implications and application prospects revealed by this study open a new door for understanding and intervening in secondary epileptogenesis. This is not only of epoch-making significance for academic research but may also have far-reaching impacts in the field of epilepsy treatment.