Dysfunction in cutaneous thermoregulatory control after spinal cord injury

NIH RePORTER · NIH · R21 · $429,000 · view on reporter.nih.gov ↗

Abstract

Abstract A dominant class of postganglionic neurons in paravertebral thoracic chain ganglia are vasoconstrictors innervating distributed organ systems including skin and muscle. For muscle, control of blood flow via vasoconstrictors operates over a narrow range. In comparison, dramatic changes in blood flow are controlled by the cutaneous vasoconstrictor system as part of a highly complex control system vitally important in homeostasis including thermoregulation. After spinal cord injuries (SCI) there is loss of cutaneous thermoregulatory control below the injury site. This can lead to detrimental effects on physiology including rendering individuals as functionally poikilothermic and prone to hypothermia and hyperthermia. This field of autonomic dysfunction after SCI is highly understudied. A completely unexplored area is whether selective neuromodulation stimulation-based control targeting of thoracic paravertebral sympathetic chain be used to control cutaneous vasoconstrictor function. Preclinical studies are required to assess targeted interventions at this site. Modulatory control of cutaneous vasoconstrictor function after SCI in innervation territories deprived of brainstem drive circuits may also be amenable for use in smart feedback-based control technologies for homeostatic control of vascular vasoconstrictor function. Presently we take advantage of the R21 exploratory research mechanism to assess whether thoracic chain ganglia can be used as a novel site for neuromodulation-based control of cutaneous vasoconstrictors. We recently developed an ex vivo adult mouse model that makes us rather uniquely positioned for comprehensive assessment of thoracic chain ganglia as a target site for therapeutic control via interfacing neuromodulation technologies. Here we leverage powerful optogenetic approaches to selectively recruit vasoconstrictors to guide optimization of electrical stimulation strategies that preferentially target activation of postganglionic over preganglionics axons. Due to their projections to prevertebral ganglia (e.g. celiac and mesenteric) recruitment of preganglionics is likely to have undesirable off target actions. Assessment of vasoconstrictor recruitment along the thoracic sympathetic chain is likely to offer ability for selective segmental control of vasomotor function. Once characterized we will compare recruitment results to those seen after high thoracic spinal cord injury at acute (first week) and more chronic stages (3 to 6 weeks). If successful, combined approaches will have determined that; (1) selective recruitment of thoracic chain paravertebral ganglia can be used to preferentially control cutaneous vasoconstrictor activity, (2) measured changes in skin temperature can be used as a feedback variable to increase cutaneous vasoconstrictor activity, and (3) whether targeting these ganglia could provide a substrate for translational neuromodulation-based approaches to control dysfunction in cutaneous thermoregula...

Key facts

NIH application ID
9958859
Project number
1R21NS116724-01
Recipient
EMORY UNIVERSITY
Principal Investigator
SHAWN HOCHMAN
Activity code
R21
Funding institute
NIH
Fiscal year
2020
Award amount
$429,000
Award type
1
Project period
2020-04-01 → 2022-09-30