Fellowship for Michael Sunshine: Promoting Cardiorespiratory Recovery via FGF Infusion and Tract Specific Activation

Abstract After the initial traumatic insult to the spinal cord, the lesion expands due to secondary cascades associated with neuroinflammation and demyelination. Fibroblast growth factors (e.g., FGF1 and FGF2) are released from axons and communicate with oligodendrocytes through FGF receptors controlling differentiation and effecting myelin thickness in mature oligodendrocytes. Indeed, providing exogenous FGFs either intrathecally or intravenously can result in smaller lesions and improved locomotor function. Though there has been little research on the effect of FGFs on cardiac or respiratory function. These studies delivering FGF1 and 2 have paved the way for research into other members of the FGF family. Recently FGF17 was identified as key driver in age-associated memory decline, and supplementation of FGF17 promoted oligodendrogenesis and restored working memory. A recent call for the study of FGFs in spinal cord injury (Fehlings 2019) led us to ask if FGF17 supplementation following spinal cord injury may promote cardiorespiratory recovery. With this preliminary data we next wondered if we could promote regeneration through repeated activation of a select tract belonging to the rostral ventral respiratory group (rVRG). Stimulation of peripheral nerves promotes regeneration and spinal epidural stimulation has demonstrated improved functional recovery especially when paired with task specific training, however the cellular substrates for this recovery are unknown. Here I propose to selectively activate the rVRG using chemogenetics to increase the activity within a specific tract. By targeting the rVRG specifically we will mitigate off target growth and increase the function of the respiratory system which could reduce attrition following SCI.