Pharmacological manipulation of CCL2/CCR2 interaction on temporal lobe epilepsy genesis and development

• Grant number: 15/11119-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2015
• End date: August 31, 2018
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Luiz Eugenio Araujo de Moraes Mello
• Grantee: Maira Licia Foresti
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Epilepsy is characterized by spontaneous recurrent seizures and is commonly associated with previous episode of traumatic brain injury or an episode of status epilepticus. Following the initial precipitating injury there is a silent period when plastic alterations occur on the nervous tissue culminating on recurrent seizures. Recently the neuroinflammation and glial role on epileptogenic plasticity has been studied. The status epilepticus induced by pilocarpine injection model mimics seizure development and typical tissue alterations of neuronal circuitry in humans, among them, significant increase in citokines and chemokines expression, such as CCL2 protein (C-C motif ligand 2 chemokine), which binds to its CCR2 receptor (CCL2 Receptor), present in neurons, astrocytes and circulating monocytes. Citokines are expressed in healthy brain tissue and participate in the neuroinflammatory response after an initial precipitating injury such as status epilepticus. These signaling molecules participate in neuroplastic changes, deterioration of damaged tissue and epileptogenesis. The study of the CCL2/CCR2 interaction blocking on epileptogenesis and seizure susceptibility can point to new treatment strategies and to improve knowledge of nervous and imune systems signalling exchange. The objective of this project is to investigate the effect of pharmacological manipulation of the CCL2/CCR2 interaction on seizure development, through analyses of changes in nervous tissue and alterations on susceptibility to seizure reinduction.

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)

FORESTI, MAIRA LICIA; ARISI, GABRIEL MAISONNAVE; CAMPBELL, JAMES J.; MELLO, LUIZ E.. Treatment with CCR2 antagonist is neuroprotective but does not alter epileptogenesis in the pilocarpine rat model of epilepsy. Epilepsy & Behavior, v. 102, JAN 2020. (16/08969-9, 15/11119-4)