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Project

Effects of single-day AIH on rebalancing excitatory and inhibitory transmission in persons with iSCI

Funder: Craig H Neilsen Foundation

Funding period
USD 150 K
Funding amount
Abstract
Spinal cord injury (SCI) disrupts sensory and motor pathways, resulting in motor impairments of the lower limb that negatively affect walking. However, most spinal cord injuries are incomplete, leaving some spared neural pathways to sensory and motor neurons that initiate and coordinate movement. Current rehabilitation therapies are limited and many do not return to community ambulation. Thus, there is a need for novel therapies that enhance endogenous mechanisms of spinal plasticity toward functional recovery. One feature of this decreased functional mobility in SCI is ankle joint spasticity, a velocity dependent increase in stretch reflex (Lance 1980) that affects up to 78% of the chronic SCI population (Skold et al., 1999). In addition to increasing pain and fatigue, spasticity negatively impacts gait performance by discordant muscle co-activation timing during gait (Fung & Barbeau 1989). Reducing spasticity is frequently a therapeutic target (Gracies et al., 1997), since reducing spastic motor behaviors such as abnormal reflex excitability may result in functional gait improvements (Scivoletto et al., 2008, Thompson et al., 2013). However, current therapeutics that reduce spasticity also maladaptively reduce neural activity and increase weakness (Thompsons & Hornby et al., 2013).Spinal plasticity is a significant contributor to motor recovery following SCI. Mild breathing bouts of low oxygen (acute intermittent hypoxia, AIH) is a novel and exciting intervention that induces spinal plasticity leading to improvements in breathing and locomotion in rats with SCI (Fuller et al., 2004, Lovett-Barr et al., 2012). The fundamental hypothesis guiding this research is that AIH elicits neural plasticity in the balance of excitatory and inhibitory transmission, thereby facilitating motor recovery in persons with iSCI. AIH strengthens excitatory transmission onto motor neurons via BDNF dependent pathways (Vinit et al., 2009, Dale-Nagle et al., 2010). However new evidence in rodent models report that BDNF dependent mechanisms also restore appropriate inhibitory transmission (Boulenguez et al., 2011, Tashiro et al., 2014), potentially contributing to reduced spasticity. Similar changes have been suggested to occur in humans with SCI, but no studies have addressed this possibility. Accordingly, the objective of this study is to determine if AIH promotes the recovery of appropriate reflex and muscle co-activity activity in humans with SCI without the undesired generalized suppression of neural excitability of current therapeutics. Such changes would indicate enhanced sensorimotor function following AIH. Findings from this project will advance our understanding of AIH-induced plasticity that may contribute to functional recovery after SCI. Assessments of muscle coactivity and reflex excitability provide a practical construct to probe downstream motor makers of the effectiveness of AIH in treating neuromotor deficits. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1106 Human Movement and Sports Science

  • FOR (ANZSRC)

    1109 Neurosciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Regenerative Medicine

  • RCDC

    Neurosciences

  • RCDC

    Perinatal Period - Conditions Originating in Perinatal Period

  • RCDC

    Rehabilitation

  • RCDC

    Spinal Cord Injury

  • RCDC

    Neurodegenerative

  • RCDC

    Pediatric

  • RCDC

    Physical Rehabilitation

  • HRCS HC

    Neurological

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science