Blood-brain barrier permeability in pilocarpine-induced epilepsy in rats

• Grant number: 08/06450-0
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2008
• End date: May 31, 2011
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Luciana Le Sueur Maluf
• Grantee: Luciana Le Sueur Maluf
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil

Abstract

Epilepsy is the most common serious brain disorder in clinical neurological, characterized by hyperactivity of neurons and brain circuits, capable of producing abnormal electrical discharges. Epidemiological data show that the temporal lobe epilepsy (TLE) is the most frequent type of epilepsy in humans, occurring in about 40-50% of patients. The TLE is the main form of epilepsy-related resistance to drug treatment, or refractory, in adults. The high incidence of refractory in TLE, and its impact on the individual life and society, has led to study of their pathophysiology, which makes the experimental models, particularly relevant. In this context, the epilepsy model induced by pilocarpine in rats becomes appropriate, since it mimics the behavioral, histological, biochemical, pharmacological and electrophysiological events that occur in TLE. Several studies have been conducted in order to know the cellular and molecular mechanisms involved in epilepsy. However, little is known about the relationship between the seizure and integrity of the blood-brain barrier (BBB). Preliminary studies showed, through the Evans Blue dye, increase of the BBB permeability to macromolecules at the enthorinal cortex of rats after 30 min of pilocarpine-induced status epilepticus. In this way, the aims of this work are: a) to evaluate, through of extracellular tracers, the integrity of BBB in several brain regions and times during the acute phase of pilocarpine-induced epilepsy model; b) to investigate, through immunohistochemistry and immunoblotting, the expression and distribution of aquaporin-4 water channel and potassium channel type inwardly rectifying Kir 4.1, both proteins involved in the ionic balance of brain's extracellular environment. This study will establish the times and brain regions of BBB breakdown during the acute phase of pilocarpine-induced epilepsy model and will improve the knowledge of the pathological processes that occur in the microenvironment surrounding the BBB failure. The results will provide subsidies for future research on the BBB's status during the latent and chronic phases of the pilocarpine model, contributing to better understanding of the pathophysiology of seizures. (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)

MENDES, NATALIA FERREIRA; PANSANI, ALINE PRISCILA; FERREIRA CARMANHAES, ELIS REGINA; TANGE, POLIANA; MEIRELES, JULIANA VIEIRA; OCHIKUBO, MAYARA; CHAGAS, JAIR RIBEIRO; DA SILVA, ALEXANDRE VALOTTA; DE CASTRO, GLAUCIA MONTEIRO; LE SUEUR-MALUF, LUCIANA. The Blood-Brain Barrier Breakdown During Acute Phase of the Pilocarpine Model of Epilepsy Is Dynamic and Time-Dependent. FRONTIERS IN NEUROLOGY, v. 10, APR 16 2019. (08/06450-0)

MENDES, NATALIA FERREIRA; NOGUEIRA MARIOTTI, FLORA FRANCA; DE ANDRADE, JOSE SIMOES; VIANA, MILENA DE BARROS; CESPEDES, ISABEL CRISTINA; NAGAOKA, MARCIA REGINA; LE SUEUR-MALUF, LUCIANA. Lactulose decreases neuronal activation and attenuates motor behavioral deficits in hyperammonemic rats. METABOLIC BRAIN DISEASE, v. 32, n. 6, p. 2073-2083, DEC 2017. (08/06450-0)