Abstract:Objective A temporal lobe epilepsy mouse model was established via intraperitoneal injection of pilocarpine (Pilo). To observe the feeding habits of mice and compare differences in body weight, fur condition, and blood ketone levels between conventional and ketogenic diet(KD) interventions, thereby establishing a standardized ketogenic feeding model. Furthermore, this study aimed to investigate the regulatory effects of a ketogenic diet on epileptic seizures, depression-like, and anxiety-like behaviors in epileptic mice. Methods Thirty-one 4-week-old male SPF-grade ICR mice (20–22 g) underwent 1-week acclimatization. Eleven mice were randomly assigned to control groups: conventional diet (CON+ND, n=5) and ketogenic diet (CON+KD, n=6). The remaining 20 mice were subjected to pilocarpine-induced status epilepticus (SE). SE model validation was performed using Racine scale scoring (≥IV), with successfully modeled mice randomly and equally allocated to epileptic model groups: standard diet (SE+ND) and ketogenic diet (SE+KD). Seizure frequency was recorded via video monitoring, while anxiety- and depression-like behaviors were assessed using the Open Field Test (OFT), Elevated Plus Maze (EPM), and Forced Swimming Test (FST). Results 1. Epilepsy Model Establishment: Among 20 mice subjected to modeling, 4 failed to reach Racine stage IV and 2 died. The remaining 14 successfully modeled mice were randomly allocated to SE+KD (n=7) and SE+ND (n=7) groups. During intervention, 2 mice died in the SE+KD group (ketogenic diet), while no mortality occurred in the SE+ND group (standard diet). 2.Ketogenic Protocol Validation: Epileptic mice exhibited lower baseline body weight than controls. No significant weight change difference was observed between dietary interventions (P > 0.05). Blood ketone levels in CON+KD group consistently exceeded 1.0 mmol/L at days 1, 7, 14, and 28. By day 2 of ketogenic feeding, 9 mice developed fur soiling with fecal matter and diarrhea, progressing to rectal prolapse in 5 severe cases by day 3. CON+ND and SE+ND mice maintained glossy coats and formed stools throughout. 3.Behavioral Outcomes: SE+KD mice showed significantly reduced seizure frequency compared to SE+ND. In the FST, CON+KD exhibited shorter immobility times than CON+ND. Conclusion Standardized ketogenic diet intervention effectively maintained therapeutic ketosis (blood ketones≥1.0 mmol/L) without significant weight impact . Notably, the ketogenic diet suppressed epileptic discharges and ameliorated anxiety- and depression-like behaviors.