Spinal cord injury: New tools to promote locomotor recovery

HR QUINTÁ

Simposio; Humboldt Colloquium "Shaping the future of German-Argentinian Scientific Cooperation - The Role of Curiosity-Driven Research"; 2018

Alexander Von Humboldt Foundation

Spinal cord injury (SCI), a traumatic pathology which affects the central nervous system, produces devastating changes often permanent in normal locomotor, sensory and autonomic function in the affected individuals. Despite extensive research in the field, the development of a successful therapeutical intervention for patients suffering this traumatic pathology remains one of the major challenges in biomedicine.The pathological process that follows a spinal cord injury involves the interplay of several factors, including different matricellular proteins and pro-inflammatory cytokines.In humans, one of the main factors contributing to functional deficits is the degeneration of spinal tissue after injury, and the concomitant trans-synaptic degeneration below the lesion site, which impairs the transmission of nerve impulses necessary for muscle activation.Currently, the approaches to promote axonal regeneration and recovery of locomotor activities involve different strategies from pharmacologic treatments to cybernetic engineering.In the present project, we have focused in the properties of Netrin-1 as a possible protein treatment to promote axonal regeneration after spinal cord injury.Netrin-1 is an evolutionarily conserved, secreted extracellular matrix protein involved in axon guidance at the central nervous system midline during neuronal development. Netrin-1 primarily acts locally by promoting growth cone adhesion (Dominici C et.,al 2017). Netrin-1 has also been shown to play a role in regenerative processes in the peripheral nervous system, where it is secreted by Schwann cells after injury to promote axonal growth. Based on the growth promoting properties of Netrin-1 both during development and regeneration, we propose the use of this protein as a therapeutic agent to promote axonal growth after spinal cord injury.Using a model of complete spinal cord transection in rats, we will assess the effects of treatment with Netrin-1 on anatomical and behavioral recovery after injury. We will use advanced microscopy techniques to evaluate axonal regeneration and target re-connection. An analysis of synaptic vesicles on ultra-thin sections of the lumbar spinal cord using optical super-resolution microscopy (STORM) will carried out. Moreover, I developed a microscopy ?clearing technique? (Quinta H et.al, 2015, 2016 and 2017) that allows to obtain tridimensional images of regenerated axons in whole tissues.In summary our study is focused on the development of an effective treatment to promote full recovery of locomotor function, with the main objective to generate a translation to the clinical medicine.