The functional role of MyD88 on neuroinflammation process and locomotor recovery after spinal cord contusion

• Grant number: 18/23775-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2019
• End date: January 31, 2021
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Alexandre Hiroaki Kihara
• Grantee: Beatriz Cintra Morena
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Spinal cord injury (SCI) is a clinical condition that that can be triggered by a traumatic (mechanical) or non-traumatic insult, possibly leading to the disruption of the communication between the central nervous system and other systems of the body. Traumatic SCI can be divided in two phases: i) the immediate consequences of mechanical trauma and ii) the activation of inflammatory response; Neuroinflammation after SCI is usually mediated by the activation of the Toll-Like Receptors (TLR) family, which is located mostly in microglia. TLRs are activated by specific pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs), directly triggering MyD88 intracellular signaling pathway. MyD88 is a cytosolic adaptor protein that mediates signal transduction initiated by most TLRs, and culminates on the expression of nuclear factor (NF)-ºB, leading to the production of inflammatory mediators that impairs tissue regeneration. However, the role of MyD88 pathway on spinal cord recovery after injury is still poorly known. Taking this into account, we aim to disclose the functional role of MyD88 on neuroinflammation, tissue regeneration, microglial phenotype and recovery of the motor function recovery after SCI. To this end, we proposed to first describe the spatiotemporal expression of MyD88 after SCI employing methods such as immunofluorescence and western blotting,. Secondly, we will focus in the functional role of MyD88, by comparison of wild type vs. MyD88 knockout mice with regards to cell death, spinal cord tissue regeneration as well as locomotor recovery. With this, we expect to disclose fundamental aspects related to neuroinflammation signaling and to contribute with the development of new strategies for the treatment of SCI. (AU)