Inflamatory response in spinal cord injury treated with VEGF and PDGF

• Grant number: 13/07824-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 15, 2013
• End date: December 14, 2013
• Field of knowledge: Agronomical Sciences - Veterinary Medicine
• Principal Investigator: Maria Angelica Miglino
• Grantee: Marcio Nogueira Rodrigues
• Supervisor: Alan Mackay-Sim
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Griffith University, Nathan, Australia
• Associated to the scholarship: 12/11560-4 - Analysis of the Therapeutic potential of cells derived from the vomeronasal organ of rabbits New Zeland, BP.DR

Abstract

The central nervous system (CNS), including the brain and spinal cord, has been considered a representative example of organs in which regeneration is difficult. Inflammatory molecules are important in healthy nervous tissue and their expression is promptly upregulated when an injury occurs. Cytokines are in neuroinflammatory response and are critical for its regulation, exerting a variety of activities. Microglia release several cytokines, chemokines, and prostaglandins, which increase the blood CNS barrier faciliting the invasion of peripheral immune cells. Few pharmacological and surgical resources are currently available to treatment of the Central Nervous Lesions, and none is able to completely reverse the damage of the initial injury. Other alternative could be the use of some factors like VEGF (Vascular Endothelial Growth Factor) and PDGF (Platelet-Derived Growth Factor). The VEGF, which is a potent stimulator and increase the angiogenesis, outside the epicenter of the lesion after spinal cord contusion injury, rescuing cells locally from ischemic death, reducing tissue loss, and improving behavioral outcomes. In the order hand, the PDGF can enhance early phagocytic activity of neutrophils and monocytes and modulate the activity of T-cells. Both growth factors target receptor tyrosine kinases expressed on macrophages/microglia, and signal through a multitude of pathways, including both the Janus kinase/signal transducer and activator of transcription and mitogen-activated protein (MAP) kinase signaling pathways which are involved in transcription of both pro- and anti-inflammatory responses in macrophages/microglia. Studies involving the treatment of the spinal cord injury with a combined application of VEGF and PDGF have been demonstrated that this therapy can be a novel therapeutic intervention for SCI, and reveal an unanticipated synergy for these growth factors whereby they modulated inflammatory processes and created a microenvironment conducive to axon preservation/sprouting. The aim of this study will better understand the effects of treatment with a combination of the VEGF and PDGF in spinal cord injury in the inflammatory response evaluating the behavior (BBB scale) of the hindlimb movements, and the tissue response to treatment through immunohistochemistry techniques using the antibodies CD43, ED1, CD3, and myelin basic protein. The hypothesis of this study is that the increase of the inflammatory response through of the angiogenesis triggered by combination of VEGF and PDGF in treatment of spinal cord injury can be induced. (AU)