Brain-derived neurotrophic factor superinduction parallels anti-epileptic-neuroprotective treatment in the pilocarpine epilepsy model

Antiepileptic drugs provide neuroprotection in several animal models of bra in damage, including those induced by status epilepticus (SE). The mechanis ms involved in this action are unknown, but neurotrophic factors such as br ain-derived neurotrophic factor (BDNF) may play a role. In this study we in vestigated the changes in BDNF levels in rats in which SE had been induced by pilocarpine injection (400 mg/kg i.p.) and continued for several hours ( unprotected group). In other animals (protected groups), SE was suppressed after 30 min by intraperitoneal injection of either diazepam (10 mg/kg) + p entobarbital (30 mg/kg) or paraldehyde (0.3 mg/kg). In diazepam + pentobarb ital-treated rats the hippocampal damage caused by SE was significantly low er (p < 0.05) than in unprotected animals. In addition, 2 and 24 h after pi locarpine injection, the levels of BDNF mRNA were moderately increased in t he unprotected group, but 'super-induced' in protected animals, especially in the neocortex and hippocampus. A time-dependent increase in BDNF immunor eactivity was also found by western blot analysis in rats treated with diaz epam + pentobarbital. In contrast, a decrease of BDNF immunoreactivity occu rred in the unprotected group. In conclusion, these results show that neuro protection induced by anti-epileptic drugs in pilocarpine-treated rats is a ccompanied by strong potentiation of BDNF synthesis in brain regions involv ed in SE.