Artificial and biological astrocytes in an acute and chronic animal model of Epilepsy

• Grant number: 22/11908-2
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2023
• End date: November 30, 2025
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Milena de Barros Viana
• Grantee: Milena de Barros Viana
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Associated researchers: Alessandra Mussi Ribeiro ; Ana Maria Ferreira de Sousa Sebastião ; Rafael Herling Lambertucci ; Sandra Cristina Henriques Vaz

Abstract

Epilepsy is a chronic neurologic disease, characterized by recurrent seizures, which are a result of excessive electrical discharges in a group of brain cells. Potential dysregulation in glutamatergic mechanisms has been a longstanding proposed mechanism in epilepsy. Increases in extracellular glutamate can lead to a buildup of glutamate in the synapse and overactivation of the glutamate receptors, resulting in excitotoxicity and ultimately, cell death. The resulting hypothesis is that a reduction in extracellular brain glutamate concentration, and thereby a reduction in glutamate excitotoxicity, can diminish epileptogenesis. Synthetic biology has emerged, during the last years, as a promising field. The focus is on the development of micro and nanostructures, including artificial cells, organelles and enzymes, the so-called micro or nanoreactors. Some of these structures are equipped with glutamate dehydrogenase and glutathione reductase, which decrease extracellular glutamate levels producing reduced glutathione. The purpose of the present study is to investigate the in vivo behavioral and neurobiological effects of these microreactors in an acute (induced by i.c.v. bicuculline administration) and in a chronic model of epilepsy (induced by intra-dorsal hippocampus administration of pilocarpine). The severity of the seizures will be evaluated in an open field according to a modified Racine scale, immediately after bicuculline or pilocarpine administration, and subsequently in three different moments after pilocarpine administration. Thirty minutes after behavioral evaluation, animals will be killed and their brain processed for the measurement of neuroinflammation, oxidative stress and neurodegeneration/neuroprotection. This project is a research collaboration between the Federal University of São Paulo and the University of Lisbon. (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)

OLIVEIRA, ROBERTO N.; CARVALHINHO-LOPES, PATRICIA S.; CARVALHO, CAROLINA P. F.; HIRATA, RAFAEL Y. S.; VAZ, SANDRA H.; SEBASTIAO, ANA MARIA; ARMADA-MOREIRA, ADAM; ROSARIO, BARBARA A.; LEMES, JESSICA A.; SOARES-SILVA, BEATRIZ; et al. Neuroprotective effects of platinum nanoparticle-based microreactors in bicuculline-induced seizures. Behavioural Brain Research, v. 465, p. 10-pg., 2024-03-26. (22/11908-2)