POSSIBLE MODULATION OF TONIC-CLONIC SEIZURES BY THE FASTIGIAL NUCLEUS

• Grant number: 24/10259-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2024
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Norberto Garcia Cairasco
• Grantee: Victor José Botta Martins
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Epilepsy is a serious neurological disease that is quite prevalent in the population, but its currently available treatments (pharmacological or surgical) are refractory in many patients, which raises the need to explore new targets. Historically, electrical stimulation of the cerebellum achieved promising results in the second half of the last century, but these were often inconsistent between patients or animal models, so that the structure practically disappeared as an interesting target for this purpose. However, with the most recent technical advances, new research has been pointing out quite consistently the great capacity of the cerebellum to modulate seizures of more than one type of epilepsy, especially with the excitation of deep nuclei of the cerebellum. Thus, the potential approach of the structure in new treatments is recovered, as well as the need for more in-depth studies. Regarding the fastigial nucleus, it is known that it has several projections not only to the diencephalon, but also to the brain stem. In this, it communicates with structures essential to the tonic-clonic seizure, such as the reticular formation, the periaqueductal gray and the superior colliculus, which is also related to the expression of endogenous anticonvulsant systems. In rats genetically selected to present audiogenic seizures, such as the Wistar Audiogenic Rat (WAR) lineage, acute exposure to intense sound stimulus (120 dB) causes tonic-clonic seizures, which essentially depend on brainstem circuits. Therefore, we propose to experiment chemical excitation (with bicuculline, a GABAA antagonist) and inhibition (with muscimol, a GABAA agonist) of the fastigial nucleus of the cerebellum of WAR rats, under the hypothesis that interventions in this nucleus can modulate tonic-clonic seizures.