Evaluation of the lack of TLR4 in the spread of the neuronal death and the functional recovery after spinal cord transection in mouse

• Grant number: 15/25346-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2016
• End date: February 28, 2017
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Vera Paschon
• Grantee: Natalia Dal Re Nogueira
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

The spinal cord damage affects many victims of car accidents, assaults, fights with weapons or knives, leading them to paraplegic or tetraplegic depending on the level of spinal cord injury. There is no perspective of treatment due to the low rate of central nervous system regeneration. Many studies showed that paraplegic and tetraplegic people, beyond disability to walk with their own legs, suffer from increased chances of urinary tract inflammation, fractures, thrombosis, cardiovascular problems, tumors, and depression. The second step after the injury is the secondary cell death with great inflammatory activity, exacerbating the lesion effects. Toll-like receptors (TLRs) are able to recognize danger-associated molecular patterns (DAMPS) as nucleic acids and proteins released from apoptotic cells in neuronal disorders, although the role of TLR4 is not completely clarified in neurons and glial cells. The aim of this project is to evaluate the neuronal damage and functional recovery after spinal cord transection of C3H/HeJ TLR4-/- mice in comparison with C3H/HePas (control) mice. The neurologic and motor function will be verified by around open field, footprints, BBB, and rotarod experiments, 1, 7, and 14 days after spinal cord transection. Molecular experiments to describe the secondary cell death spread and TLR4 distribution in the spinal cord after injury, as TUNEL, immunofluorescence, and real-time PCR, will be conducted with a spinal cord segment removed from animals submitted to euthanasia 1, 7 and 14 days after lesion.