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 3rd cervical spinal level (C3) showed immediate alterations in laryngeal activity. These alterations persisted for 4 hours (testing duration). The serotonin (5‐HT1A) 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% CO2). 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.
Videofluoroscopy is the gold standard for clinical measurement of swallow disorders (dysphagia). Patients are presented with foods and liquids of varying consistencies in order to evaluate the risk of aspiration. The Modified Barium Swallow Impairment Profile (MBSImP) was developed in 2008 and has since become the primary tool to define the degree of dysphagia impairment. In order to determine the utility of the MBSImP in animals with cervical spinal cord injury, animals were presented with tuna water and pate cat food laced with 40% barium sulfate by volume. Data was collected using a miniature c‐arm collecting at 30 frames per second, and exams were performed pre and post cervical spinal cord injury. Out of the 17 components scored on the MBSImP, only 10 components are usable for animals. Additional components/variables are needed due to their anatomical and physiological differences. More specifically, the pharyngeal phase of the swallow in cats shows a threshold in the pharyngeal distention before a full swallow is completed as well as numerous “rocking” motions to transport the bolus posteriorly from the oral cavity. Another difference shows that component 9 (Anterior Hyoid Excursion) is harder to detect due to the slight displacement of the hyoid. However, we did determine that penetration and aspiration could be reliably detected post‐injury using the 30‐frames per second recording. These results support the use of clinical techniques; however, the addition of continuous variables would assist in the measurement of small changes across time. Support or Funding Information This work was supported by NIH grant NS110169 and the Craig H. Neilsen Foundation Pilot Research Grant 546714.
Cervical spinal cord injuries (cSCIs) can cause swallow disorder (dysphagia), potentially resulting in aspiration and pneumonia. Dysphagia is characterized by disruption of the swallow motor pattern, which involves sequential activation of muscles that propels the bolus into the esophagus while avoiding the airway. Normal swallow includes diaphragm activity that generates negative pressure, drawing the bolus into the esophagus. Centers in the brainstem control the swallow patterns. Thus, despite reports of dysphagia in some patients with cSCI, little consideration has been given to the potential contributions of spinal circuitry to swallow. We aim to characterize swallow dysfunction in cats with cSCI. Using EMG to record breathing patterns, water‐induced swallow in pentobarbital‐anesthetized spontaneously breathing cats is captured before and after acute high cervical hemisections (at C2 or C3). EMGs are recorded from the mylohyoid, thyrohyoid, thyroarytenoid, thyropharyngeus, cricopharyngeus (upper esophageal sphincter), and diaphragm muscles, and trans‐diaphragmatic pressure is measured by monitoring esophageal and stomach pressures. After hemisection, swallow is dramatically altered, as indicated by a dysfunctional swallow motor pattern. Coordinated, sequential muscle activation necessary for proper movement of a bolus through the pharynx is lost, esophageal pressure is positive rather than negative due to reduced activation of the diaphragm, and upper airway EMG activity increases. These alterations in behavior‐specific muscle recruitment patterns are profoundly dysphagic, indicating that disruption of spinal circuits in the high cervical spinal region can produce major dysfunction in swallow motor patterns. This work may inform screening and treatment protocols of the cSCI patient population, in which dysphagia is likely to be underdiagnosed. Support or Funding Information NIH grants HL 111215, NS 110169 and OT20D001983, the Craig H. Neilsen Foundation Pilot Research Grant 546714, Kentucky Spinal Cord and Head Injury Research Trust, the Commonwealth of Kentucky Challenge for Excellence, VA RR&D B9249S and the Rebecca F. Hammond Endowment.
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