Comorbidity of cardiorespiratory and locomotor dysfunction following cervical spinal cord injury in the rat.

Cervical spinal cord injury interrupts supraspinal pathways innervating thoracic sympathetic preganglionic neurons and results in cardiovascular dysfunction. Both respiratory and locomotor functions were also impaired due to damages of motoneuron pools controlling respiratory and forelimb muscles, respectively. However, no study has investigated autonomic and somatic motor functions in the same animal model. The present study aimed to establish a cervical spinal cord injury model to evaluate cardiorespiratory response and locomotor activity in unanesthetized rats. Cardiovascular response and respiratory behavior following laminectomy or cervical spinal contusion were measured using noninvasive blood pressure analyzer and plethysmography systems, respectively. Locomotor activity was evaluated by an open-field test and a locomotor rating scale. The results demonstrated that mean arterial blood pressure and heart rate were significantly reduced in contused rats compared with uninjured rats at the acute injured stage. Tidal volume was also significantly reduced during the acute and subchronic stages. Moreover, locomotor function was severely impaired, evidenced by decreasing moving ability and locomotor rating scores from the acute to chronic injured stages. Retrograde neurotracer results revealed that cervical spinal cord injury caused a reduction in number of phrenic and triceps motoneurons. Immunofluorescence staining revealed a significant attenuation of serotonergic, noradrenergic, glutamatergic, and GABAergic fibers innervating the thoracic sympathetic preganglionic neurons in chronically contused rats. These results revealed the pathological mechanism underlying the comorbidity of cardiorespiratory and locomotor dysfunction following cervical spinal cord injury. We proposed that this animal model can be used to evaluate the therapeutic efficacy of potential strategies to improve different physiological functions.NEW & NOTEWORTHY The present study establishes a preclinical rodent model to comprehensively investigate physiological functions under unanesthetized condition following cervical spinal cord contusion. The results demonstrated that cervical spinal cord contusion is associated with impairments in cardiovascular, respiratory, and locomotor function. Respiratory and forelimb motoneurons and neurochemical innervations of sympathetic preganglionic neurons were damaged following injury. This animal model can be used to evaluate the therapeutic efficacy of potential strategies to improve different physiological functions.

Modulation of the extrinsic tongue muscle activity in response to bronchopulmonary C-fiber activation following midcervical contusion in the rat.

This study was designed to investigate extrinsic tongue muscle activity in response to bronchopulmonary C-fiber activation following midcervical spinal contusion in the rat. Esophageal pressure and electromyogram of the extrinsic tongue muscles (genioglossus and hyoglossus) were monitored before and after inhalation of capsaicin (25 and 100 µg/mL) at the acute (3 days), subchronic (12-16 days), and chronic (52-65 days) injured stages following unilateral midcervical spinal contusion. Three days after injury, the preinspiratory burst amplitude of the extrinsic tongue muscle at baseline was significantly greater in midcervical spinal-contused animals than in sham animals. At this time, capsaicin induced a significant reduction in both preinspiratory and inspiratory activity of the extrinsic tongue muscle in sham but not contused animals at the acute stage. During the chronic injured stage, capsaicin at 100 µg/mL induced stronger suppression of preinspiratory genioglossus muscle activity in the contused animals than in sham animals. These results demonstrated that cervical spinal cord injury alters upper airway motor outputs and their reflex modulation by bronchopulmonary C-fibers. The compensatory increase in respiratory activity of the extrinsic tongue muscle early after cervical spinal cord injury may help to maintain upper airway patency. However, under the condition of chronic cervical spinal cord injury, the increased suppression of genioglossus muscle activity by bronchopulmonary C-fiber activation may increase the risk of airway obstruction following chronic cervical spinal cord injury.NEW & NOTEWORTHY Tongue muscle activity plays an important role in the regulation of upper airway patency. This study aimed to investigate the respiratory activity of the extrinsic tongue muscle in response to capsaicin-induced bronchopulmonary C-fiber activation following cervical spinal cord contusion. Midcervical spinal-contused animals exhibited a greater baseline preinspiratory burst amplitude of the extrinsic tongue muscle and were resistant to inhaled capsaicin-induced reduction of respiratory tongue muscle activity at the acute injured stage. However, inhalation of capsaicin caused a more severe attenuation of preinspiratory activity of the extrinsic tongue muscle at the chronic injured stage. These results suggest that the upper airway may be predisposed to collapse in response to bronchopulmonary C-fiber activation following chronic cervical spinal cord injury.