A Ketogenic Diet may Improve Cognitive Function in Rats with Temporal Lobe Epilepsy by Regulating Endoplasmic Reticulum Stress and Synaptic Plasticity.

A ketogenic diet (KD) is often used in the treatment of refractory epilepsy. Many studies have found that it also has a positive impact on cognitive comorbidities, but the specific mechanism remains unclear. In many disease models, endoplasmic reticulum stress (ERS) and synaptic plasticity is considered a new therapeutic target for improving cognitive impairment, and it has become a research focus in recent years. Recently, studies have found that a KD has a certain regulatory effect on both ERS and synaptic plasticity, but this result has not been confirmed in epilepsy. To investigate the effect of a KD on ERS and synaptic plasticity. In this study, a rat model of temporal lobe epilepsy (TLE) induced by lithium chloride-pilocarpine was used. After the model was successfully established, the rats in each group were fed a normal diet or a KD for 28 days, and the effect of a KD on the latency and seizure frequency of spontaneous recurrent seizures (SRSs) was observed via video monitoring. Subsequently, a Morris water maze was used to evaluate the spatial learning and memory abilities of the rats in each group; the ultrastructure of the ER and the synapses of the hippocampus were observed by transmission electron microscopy, and the dendritic spine density of the hippocampus was analysed by Golgi staining. Long-term potentiation (LTP) was used to detect the synaptic plasticity of the rats' hippocampi, and the expression of ERS-related proteins and synapse-related proteins was detected by Western blotting. A KD effectively reduced the frequency of SRSs in rats with TLE and improved their learning and memory impairment. Further investigations found that a KD inhibited the up-regulation of glucose-regulated protein 78, phospho-protein kinase-like ER kinase, phosphorylated α subunit of eukaryotic initiation factor 2, activating transcription factor 4 and C/EBP homologous protein expression in the hippocampi of rats with TLE and protected the ultrastructure of the neuronal ER, suggesting that a KD suppressed excessive ERS induced by epilepsy. Concurrently, we also found that a KD not only improved the synaptic ultrastructure and increased the density of dendritic spines in rats with TLE but also reversed the epilepsy-induced LTP deficit to some extent. More importantly, the expression of postsynaptic density protein 95, synaptotagmin-1 and synaptosomal-associated protein 25 in the hippocampi of rats with epilepsy was significantly increased after KD intervention. The study findings indicate that a KD improves learning and memory impairment in rats with epilepsy, possibly by regulating ERS and synaptic plasticity.

Effect of low­frequency repetitive transcranial magnetic stimulation on cognitive function in rats with medial temporal lobe epilepsy.

Epilepsy, especially the medial temporal lobe epilepsy (TLE), can result in cognitive impairment. Low­frequency repetitive magnetic stimulation (rTMS) has been verified to suppress neural excitability and reduce seizures. Given its potential in modifying cortical activity, we aimed to investigate its impact on cognitive function in the context of epilepsy, a condition where the use of rTMS has not been extensively explored. However, the influence on cognitive function has not yet been investigated. Therefore, this study aimed to investigate the effects of low­frequency rTMS on cognitive improvement in epileptic rats. Rats used in this study were randomly divided into five groups: the sham group, the epilepsy group, and three epilepsy groups treated with rTMS at different frequencies. Each group underwent the Morris water maze test to investigate hippocampus­dependent episodic memory, to evaluate their cognitive performance. Further assessments included patch clamp and western blot techniques to estimate the synaptic function in the hippocampus. Comparison between groups showed that low­frequency rTMS significantly reduced spontaneous recurrent seizures and improved spatial learning and memory impairment in epileptic rats. Additionally, rTMS remodeled the synaptic plasticity affected by seizures and notably enhanced the expression of AMPAR and synaptophysin. Low­frequency rTMS can antagonize the cognitive impairment caused by TLE, and promote synaptic connections.