Exploring neurovascular unit adaptations in the regulation of apoptosis and glial response after brain injury

• Grant number: 22/04258-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2023
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marimélia Aparecida Porcionatto
• Grantee: Lina Maria Delgado Garcia
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 18/12605-8 - Development of brain-on-a-chip microplataforms for in vitro modeling of the central nervous system, AP.TEM
• Associated scholarship(s): 24/03057-8 - Integration of single-cell tracing tools into neuron-glia networks to study glial response and neurovascular unit adaptations, BE.EP.PD

Abstract

The Neurovascular Unit (NVU) is a multicellular structure whose primary function is the regulation of vascular permeability and blood flow, allowing the supply of oxygen and glucose for the functioning of the neural network. Traumatic brain injury (TBI) compromises the integrity of the NVU and causes a rupture in the neuron-astrocyte-vasculature communication, causing the dysfunction of the blood-brain barrier and activation of the inflammatory response and apoptosis. Galectins are an evolutionarily conserved group of proteins with carbohydrate-binding domains. Galectins participate in various biological processes, ranging from proliferation, migration, and cell differentiation to cell survival and apoptosis. Previous analysis showed the participation of Gal3 in astrocyte reactivation response. Furthermore, Gal3-/- mouse proteomic analysis showed the contribution of several biological responses, including but not limited to the regulation of apoptotic signaling and glial response. In this context, this project aims to study the biochemical and cellular adaptations of the NVU in apoptotic signaling regulation, neural death, and glial response after a brain injury model. In the first two stages of this project, we will use endothelial cells, astrocytes, and neurons primary cultures from Gal3-/- and control mice for NVU in vitro modeling. Later, in the final stage, we will use human- endothelial cells and astrocytes differentiated-iPSCs. In this project, we expect to gain an integrative view of Gal3 function, apoptotic signaling activation/regulation mechanisms, and glial response in the NVU context. In addition, we also expect to validate our findings in the NVU- iPSCs human model. Understanding the mechanisms involved in the organism´s multicellular and molecular response to brain injury is fundamental for developing new therapeutic strategies.

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)

DELGADO-GARCIA, LINA M.; OJALVO-SANZ, ANA C.; NAKAMURA, THABATTA K. E.; MARTIN-LOPEZ, EDUARDO; PORCIONATTO, MARIMELIA; LOPEZ-MASCARAQUE, LAURA. Dissecting reactive astrocyte responses: lineage tracing and morphology-based clustering. Biological Research, v. 57, n. 1, p. 16-pg., 2024-08-14. (19/09183-7, 16/19084-8, 18/12605-8, 22/04258-1)