Epileptogenesis, biomarkers and post-traumatic epilepsy

• Grant number: 18/24561-5
• Support type: Research Projects - Thematic Grants
• Duration: February 01, 2020 - January 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal researcher: Maria da Graca Naffah Mazzacoratti
• Grantee: Maria da Graca Naffah Mazzacoratti
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Pesquisadores principais:( Atuais ): Beatriz de Oliveira Monteiro ; Síntia Iole Nogueira Belangero
• Pesquisadores principais:( Anteriores ): Maria da Graca Naffah Mazzacoratti
• Assoc. researchers: Almir Ferreira de Andrade ; Carla Baise ; Claudia da Costa Leite ; Eliana Garzon ; Manoel Jacobsen Teixeira ; Marimélia Aparecida Porcionatto ; Paulo Eduardo Luiz de Mattos ; Síntia Iole Nogueira Belangero ; Wellingson Silva Paiva
• Associated scholarship(s): 22/01718-1 - Evaluation of the effects of biperiden on convulsive behavior and microglial activation after induction of traumatic brain injury in rats, BP.IC; 21/14564-0 - Search for miRNAs from exosomes relevant to epileptogenesis, BP.IC; 20/13586-7 - Evaluation of biperiden administration in post-traumatic brain injury: post-processing of functional magnetic resonance imaging, BP.TT; 20/03377-1 - Evaluation of biperiden administered after traumatic brain injury: research management and data analysis, BP.TT; 17/05242-3 - STUDY OF THE ANTICONVULSANT EFFECT OF CANNABIDIOL AFTER TRAUMATIC BRAIN INJURY., BP.PD

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

A.C. MOSINI; M.L. CALIÓ; M.L. FORESTI; R.P.S. VALERIANO; E. GARZON; L.E. MELLO. Modeling of post-traumatic epilepsy and experimental research aimed at its prevention. Brazilian Journal of Medical and Biological Research, v. 54, n. 2, p. -, 2021. (18/24561-5)

BENASSI, SIMONE KASTROPIL; SILVA MACEDO ALVES, JULIETA GONCALVES; GUIDORENI, CRISTIANE GORGATTI; MASSANT, CRISTINA GONCALVES; QUEIROZ, CLAUDIO M.; GARRIDO-SANABRIA, EMILIO; DE SOUZA LODUCA, RAFAEL DUARTE; SUSEMIHL, MARIA ALICE; PAIVA, WELLINGSON SILVA; DE ANDRADE, ALMIR FERREIRA; et al. Two decades of research towards a potential first anti-epileptic drug. SEIZURE-EUROPEAN JOURNAL OF EPILEPSY, v. 90, n. SI, p. 99-109, AUG 2021. (18/24561-5)