Gender-Specific Effects of Chronic Y-27632 Administration On Spike-and-Wave Discharges in Genetic Absence Epilepsy Rats

Background/Purpose: The acute intracerebroventricular (i.c.v.) injection of a Rho kinase inhibitor Y-27632 has been demonstrated to reduce the total seizure duration and mean duration of seizures in male GAERS (Genetic Absence Epilepsy Rats from Strasbourg). The purpose of this research is to determine the chronic use of five days will effect the spike-and-wave discharges (SWD) of absence epilepsy in female GAERS as well as to show if there is any difference in the expression of SWDs between female and male GAERS. Methods: Five female weighing about 150-350 grams, and male GAERS were used in experiments. Stereotaxic surgery was performed to insert EEG recording electrodes over the fronto-parietal cortices under anesthesia. Female GAERS were injected with the substance Y-27632 intraperitoneally over the course of five days rats, and compared to the baseline EEG of the same animals. In addition male and female GAERS baseline SWD characteristics were analyzed using EEG recordings and paired and unpaired t-tests were performed. Results: Total and mean SWD duration, and the number of SWDs did not significantly differ when applied to female GAERS. Although a trend of reduced total duration was observed in female rats it was not statistically significant. For the comparison of the mean duration and number of SWDs between the female and male GAERS, a significant difference was observed (p< 0.05). While the mean duration for SWDs is shorter in duration in females (t(8) = 3.23, p = 0.01), the number of SWDs were more in females in comparison to male GAERS (t(8) = 2.97, p = 0.02). Conclusion: This study highlights the intricate relationship between gender, epilepsy, and pharmacological interventions. Although some outcomes did not reach statistical significance, trends suggest potential gender-related differences in SWD response to Y-27632 or SWD expression in general. The administration route may not be as effective in intraperitoneal route as in i.c.v. Further experiments can be performed by changing the route of administration.