The effect of mannitol on brain electrical activity in the experimental status epilepiticus model and the role of increased permeability in the blood brain barrier in this effect

Mannitol infusion causes dehydration of brain vascular endothelial cells and enlargement of tight junctions. This provides an increase in the permeability of the barrier. In addition, the antiseizure effect of extracellular hyperosmolarity is known, but the appropriate therapeutic dose for this effect is uncertain. This study investigates the effect of mannitol on brain electrical activity and the effect of blood-brain barrier on valproic acid and phenytoin permeability in penicillin-induced status epilepticus model. Penicillin G was injected into the somatomotor cortex of the rats under urethane anesthesia and an epileptic focus was created. Rats; were divided into intravenous infusion groups as control(2ml SF, 1st group), mannitol(1.5g/kg, 2nd group), phenytoin(50mg/kg, 3rd group), mannitol+phenytoin(1.5g/kg+25mg/kg, 4th group), VPA(400mg/kg, 5th group), mannitol+VPA(1.5gr/kg+200mg/kg, 6th group). Infusions were administered 30 minutes after penicillin G injection and their effects on epileptiform activity were evaluated by electrocortigography (ECoG) recordings. The effect of mannitol on BBB was evaluated by phenytoin and VPA levels in blood and CSF samples. Statistical analyses were evaluated by One-Way ANOVA, Independent-Samples T-test and Mann-Whitney U test according to whether they showed normal distribution. When the ECoG recordings in the penicillin-induced status epilepticus model were evaluated, no significant difference was found between the groups. In the results of the samples; There was no significant difference in CSF/serum ratio, serum and CSF values between the 3rd and 4th groups. While there was no significant difference in CSF/serum ratio and CSF value in the 5th and 6th groups, the serum value in the 5th group was significantly higher than in the 6th group. This study suggests that phenytoin, VPA, mannitol, mannitol+VPA and mannitol+phenytoin do not affect epileptiform activity in the penicillin-induced status epilepticus model. It also suggests that there may be a pharmacokinetic interaction between phenytoin and mannitol, and that mannitol may increase the BBB permeability of VPA. More studies are needed to determine the suitability of the penicillin-induced status epilepticus model for antiseizure drug efficacy studies, to determine the antiseizure activity of mannitol and to determine its effect of mannitol on BBB. Keywords: penicillin, status epilepticus, mannitol, valproic acid, phenytoin