Hypercapnia respiratory training to enhance plasticity after cervical spinal cord injury

Margo Lillian Randelman

doi:10.17918/00000693

Cervical spinal cord injury (SCI) often damages the phrenic motor circuit that innervates the diaphragm. Injury to this circuit results in severe respiratory dysfunction - one of the leading causes of morbidity and mortality in SCI individuals. While spontaneous functional plasticity does occur following cervical SCI, the extent is limited, and diaphragm paresis persists, resulting in an urgent need for novel therapeutic approaches. This research aims to address the need for improving respiratory function by enhancing and directing the intrinsic plasticity within phrenic circuitry following cervical SCI. A novel, non-invasive respiratory training called Intermittent Hypercapnia (IHc) will be used to increase diaphragm activity and enhance anatomical and functional plasticity following a clinically relevant C3/4 contusion injury in the adult rat. Aim1 will determine the efficacy of IHc training at promoting directed supraspinal anatomical plasticity into phrenic circuitry and the role of this anatomical plasticity in improving respiratory function. Other respiratory training paradigms have demonstrated enhanced serotonergic growth and plasticity within the phrenic circuit following training. IHc, however, presents a novel and translational training paradigm for enhanced neuroplasticity, which will be quantified through respiratory bulbospinal circuitry and serotonergic growth within the phrenic circuit. Aim 2 will examine the anatomical recruitment of specific populations of phrenic interneurons and their contribution to functional recovery following IHc training. While previous work within our lab and others has demonstrated the presence of interneurons within phrenic circuitry, it is unknown how IHc training will affect interneuron recruitment, the types of interneurons that are recruited, and how they contribute to respiratory recovery. These studies will test the hypothesis that enhancing and directing the intrinsic plasticity into phrenic circuitry through daily Acute Intermittent Hypercapnia training (IHc) will result in greater anatomical and functional plasticity and improved phrenic motor recovery. Overall, this work will significantly contribute to the field by thoroughly evaluating behavioral, molecular, and anatomical effects of a novel respiratory training paradigm (IHc) and its effect on respiratory recovery following a C3/4 spinal cord injury.

Hypercapnia respiratory training to enhance plasticity after cervical spinal cord injury

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Hypercapnia respiratory training to enhance plasticity after cervical spinal cord injury

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