Epileptogenesis, biomarkers and post-traumatic epilepsy

Abstract

Traumatic brain injury (TBI) is a public health problem, with considerable social and economic burden. TBI is one of the most important causes of secondary epilepsy. TBI leads to post-traumatic epilepsy (PTE) most likely by means of direct damage to the brain parenchyma, which in turn leads to neurodegeneration and inflammatory responses, as well as molecular, structural and electrophysiological changes (such as high frequency oscillations and cortical spreading depression). All of these changes produce anomalous circuitries that will occasionally lead to hyperexcitability. Although different classes of drugs and/or surgical procedures constitute therapeutic options for TBI damage, there is currently no treatment that prevents the development of PTE. In the course of 2 decades of experiments our group tested biperiden in order to move forward with a deeper investigation. Biperiden is an anticholinergic molecule, commonly used to treat Parkinson's disease. Biperiden was able to reduce the frequency and severity of spontaneous seizures and increase the latency for the first spontaneous seizure in the pilocarpine model of epilepsy. In other words, biperiden showed to be a potential candidate to be further investigated as a disease-modifying agent after TBI. In this study, we aim to investigate the safety and efficacy of biperiden in adult patients, who suffered moderate and severe TBI. Patients will be treated during the acute phase, just after trauma, as a means to avoid the epileptogenic process. Assuming we confirm our hypothesis this project will allow for: 1) characterizing a mechanism of action for treating this condition; 2) this, in turn, would open the opportunity to develop and test new molecules; 3) provide an affordable treatment option (the use of biperiden in this condition would characterize second use of a drug already available at SUS). (AU)