Src Family Kinase Inhibitor: Saracatinib as a Potential Therapeutic Agent for Epileptogenesis

Abstract

<p>Spontaneous recurrent seizures are the hallmark of epilepsy, a common neurological disorder. The condition is often caused by insult to the brain that spurs a prolonged seizure- status epilepticus (SE). Epilepsy can be highly resistant to medication in cases where brain insult is in the form of chemical nerve agent exposure. Src family kinases (SFK) have recently been identified as a mediator of neuroinflammation. This study utilizes the SFK inhibitor Saracatinib as a viable post-treatment for epileptogenesis following initiation of SE by the organophosphate nerve agent, Soman. This study tested 20 mg/kg of Saracatinib once a day for a week. Saracatinib following Soman administration minimally affected spiking activity but did not affect convulsive seizures compared to vehicle-treated animals 10 to 15 weeks post treatment. Saracatinib-treated rats had statistically significant fewer spikes on days 9, 22, 23, and 30. Vehicle-treated rats had statistically significant higher spikes than the mild group on days 30-34. A different dosing regimen for a prolonged period may have a significant outcome with respect to these parameters. Other parameters such as MRI, behavioral, and histological tests should be considered to draw meaningful conclusions of Saracatinib treatment.</p>