Acute and Chronic Laryngeal Deficits Following Cervical Spinal Cord Injury

Laryngeal dysfunction is a common symptom following cervical spinal cord injury (cSCI) and currently there are no effective pharmacological interventions or behavioral treatments. The larynx is the primary valve controlling entrance into the trachea and lungs via opening and closing of the vocal folds. Although not well studied following cSCI, it is understood that laryngeal deficits during swallow often produce aspiration of food/liquid, significantly increasing risk of pneumonia. Our previous terminal electrophysiology experiments using freely breathing sodium pentobarbital anesthetized cats with acute hemisections at the 3 rd cervical spinal level (C3) showed immediate alterations in laryngeal activity. These alterations persisted for 4 hours (testing duration). The serotonin (5‐HT 1A ) receptor agonist 8‐OH‐DPAT was delivered via the vertebral artery at low (3 □g/kg) and/or high (30 □g/kg) doses. This agonist altered behavior‐specific muscle recruitment patterns. In particular, the high dose restored laryngeal activity across breathing and swallow, which could be reversed with the competitive antagonist WAY100635 (0.5 mg/kg). In the current study, we tested if alterations seen acutely in laryngeal activity persist chronically, and if the 8‐OH‐DPAT clinical‐correlate buspirone (Buspar) would produce similar therapeutic results. Adult female cats underwent C3 hemisections and recovered for 4 or 8 weeks. Laryngeal endoscopy was performed weekly under isofluorane (3%) during normocapnia and hypercapnia (5% CO 2 ). Asynchronous vocal fold movement was seen in all animals, defined by unilateral movement delays, and the extent of opening and closing of the glottis became variable. In a subset of animals, oral buspirone (5 mg) was given with food. One hour later, repeat endoscopic evaluation revealed full resolution of laryngeal function with synchronized movements during normocapnia and hypercapnia. Most importantly, with termination of buspirone dosing, laryngeal dysfunction returned. This work shows that the anesthetized preparation effectively identifies upper airway dysfunction early and chronically after C3 SCI, and that it can be used as a pre‐clinical model for novel therapeutic interventions. Results also indicate that buspirone is a high‐priority target for additional investigation as a therapeutic intervention after cSCI. Support or Funding Information This work was supported by NIH grants HL 111215, HL 103415 and OT20D001983, the Craig H. Neilsen Foundation Pilot Research Grant 546714, Veterans Affairs Rehabilitation, Research and Development RCSB9249S (DRH), Kentucky Spinal Cord and Head Injury Research Trust, Rebecca F. Hammond Endowment (DRH), and the Commonwealth of Kentucky Challenge for Excellence.