We aimed to investigate the effect of the P2X7 purinergic receptor antagonist brilliant blue G (BBG) on epileptic seizures, brain oxidative stress and neuronal injury induced in rats by pentylenetetrazole (PTZ). Rats received repeated intraperitoneal (i.p) injections of PTZ till the development of status epilepticus. BBG (50 or 100 mg/kg) was i.p. administered 30 minutes before starting PTZ injections. Seizure scores, the latency time and the PTZ dose for each group required to reach status epilepticus were determined. Brain kevels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), paraoxonase-1 (PON-1), brain derived neurotrophic factor (BDNF), interleukin-6 (IL-6) and chemerin were determined and histopathological examination done. PTZ induced significant increases in brain MDA and NO by 72.5% and 194.1%, respectively compared with the saline control. GSH, PON-1 activity and BDNF decreased by 41.4%, 39.8% and 33.4% while IL-6 and chemerin increased by 13.3% and 26.8%. The PTZ-induced changes in MDA, NO, GSH and PON-1 were significantly reduced by treatment with BBG which also significantly decreased IL-6 and BDNF levels. BBG (50 or 100 mg/kg) decreased the mean total seizure score by 82% and 87%, respectively. Scores for myoclonic jerks were reduced by 94.0% and 97.6% and that for generalized tonic-clonic seizures by 75%. BBG increased the threshold dose of PTZ by 66.7% and 106.7% and the latency time for status epilepticus by 118%. BBG exerts anticonvulsant and neuroprotective effects, at least in part by decreasing brain oxidative stress, BDNF and neuroinflammation.