Walaa Obydah - Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura (۳۵۵۱۶), Egypt.
Ahmed Fathi Abouelnaga - Department of Animal Husbandry and Development of animal wealth, Faculty of Veterinary Medicine, Mansoura University, Mansoura ۳۵۵۱۶, Egypt.
Marwa Abass - Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Mansoura University, Mansoura ۳۵۵۱۶, Egypt.
Somaya Saad - Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura (۳۵۵۱۶), Egypt.
Asmaa Yehia - Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura (۳۵۵۱۶), Egypt.
Omar Abd-Alhakem Ammar - Basic Science Department, Delta University for Science and Technology, Gamasa, Egypt.
Alaa Mohamed Badawy - Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, ۳۵۵۱۶, Egypt.
Mohie Mahmoud Ibrahim - Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, ۳۵۵۱۶, Egypt.
Abdelaziz Mohamed Hussein - Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura (۳۵۵۱۶), Egypt.

Background: To examine the impact of aging on the response of rats to pentylenetetrazole (PTZ)-induction of epilepsy and the possible role of oxidative stress and nuclear factor erythroid ۲-related factor ۲ (Nrf۲)/ heme oxygenase (HO)-۱ pathway in this response. Methods: Forty male albino rats were equally allocated into ۴ groups; ۱) Young control (YC) group, aged ۸-۱۲ weeks, ۲) Old control (OC) group, aged ۲۴ months, ۳) PTZ-Young group: young rats received PTZ (۵۰ mg/Kg, i.p. every other day) for ۲ weeks and ۴) PTZ-Old group: as group ۳ but rats were old. The seizure score stage and latency to the first jerk were recorded in rats. Redox state markers in brain tissues including malondialdehyde (MDA), catalase and total antioxidant capacity (TAC) were evaluated. Also, the expression of Nrf۲ and HO-۱ genes were measured in the brain tissues. Results: Old rats showed an early and a significant rise in the seizure score with PTZ administration and a significant drop in the seizure latency compared to young rats (P <۰.۰۱). Also, old rats showed a significantly higher MDA concentration and a significantly lower TAC and catalase activity than young rats (P <۰.۰۱). Moreover, the expression of Nrf۲ and HO-۱ was significantly lowered in old rats compared to young rats with PTZ administration (P < ۰.۰۱). Conclusions: Aging increases the vulnerability of rats to PTZ-induced epilepsy. An effect might come down to the up-regulation of oxidative stress and the down regulation of antioxidant pathways including Nrf۲ and HO-۱.

Aging, Epilepsy, HO-۱, Nrf۲, Oxidative stress, Pentylenetetrazole (PTZ).