Failure of the Blood Brain Barrier is Auxiliary Factor in the Effectiveness of Hydrophilic Anticonvulsant Drug

AC1 (AC1L1V0B) as soluble phenol possesses a wide range of pharmacological activities including anti-inflammatory and anti-oxidant effects. In Present study, we want to evaluate the correlation between the blood-brain barrier (BBB) destruction during epileptic seizures and amount of entry hydrophilic anti-inflammatory drug such as AC1 in the central nervous system. In order to examine the probability of the AC1 passage from blood brain barrier (BBB), HPLC analysis was used to assess the levels of AC1 in hippocampal tissues. Hippocampal samples from three experimental groups of NMRI mice including AC1 (50 mg/kg)+PTZ, AC1 (50 mg/kg) and intact was extracted. After evaporation of extraction solvent at 4 ºC, 100 ml mobile phase was added and 20 ml of final solution was injected into the HPLC apparatus. The HPLC column was reverse phase C8 column (4.6 mm i.d * 250 mm) and the mobile phase was consisted of mixture of methanol/ acetonitrile (50:50). The flow rate was adjusted to 1 ml/min and the eluent was detected using ultraviolet (UV) detector at wavelength of 292 nm. Gene expression analysis was carried out to evaluate the effect of AC1on expression of inflammatory mediators in hippocampus. HPLC analysis showed that there were not any detectable levels of AC1 in the hippocampus of intact animals. Interestingly, in comparison with the AC1 receiving animals, the AC1 content significantly increased in AC1 +PTZ treated animals (p < 0.001). The mRNA levels of TNF-alpha, IL-6 were significantly downregulted in animals under treatment of AC1. The correlation between epileptogenesis, seizures and abnormal BBB was confirmed by previous report. Accumulating evidences indicated that PTZ administration could be regarded as the important factors to induce cell death pathway and parenchymal cellular damage. In parallel with these findings, it seems that change the permeability of the BBB by inflammatory factors can causes more hydrophilic anticonvulsant drugs passage through the BBB