Increasing Sensory Neuron Regeneration in the Injured Spinal Cord with Acute Intermittent Hypoxia
Abstract
The poor intrinsic regenerative capacity of mature central nervous system (CNS) neurons combined with the barrier imposed by the inhibitory environment is a major contributor to regeneration failure and permanent disabilities following spinal cord injury (SCI). Targeting both neuron-intrinsic and -extrinsic factors has been shown to improve axon regeneration. My laboratory has focused on elucidating how peripheral neurons regenerate, with the goal to identify novel therapeutic strategies for the treatment of CNS injuries. We discovered that the transcription factor HIF-1alpha stimulates axon regeneration in sensory neurons via transcriptional and epigenetic mechanisms. We found that mice undergoing Acute Intermittent Hypoxia (AIH ) treatment display enhanced axon regeneration in sensory and motor neurons in a HIF-1alpha dependent manner. We hypothesize that AIH stimulates the regenerative capacity of injured neurons in the spinal cord, via transcriptional and epigenetic mechanisms. Because combinatorial approaches to neutralize the inhibitory environment and to boost the intrinsic neuronal growth capacity provide greater recovery, we also hypothesize that AIH paired with approaches to relieve CSPG-mediated inhibition can stimulate functional recovery following contusive SCI. The scope of the research is to determine if AIH treatment mimics the epigenomic changes elicited by peripheral injury and stimulates axon regeneration of dorsally ascending sensory axons following SCI. We also propose to determine if AIH combined with modulation of the CSPG receptor PTPsigma have synergetic effects on functional recovery following SCI.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1086516
Entities
People
- Valeria Cavalli
Organizations
- Washington University in St. Louis