Ampakines stimulate diaphragm activity after spinal cord injury

2021 ◽  
Author(s):  
Sabhya Rana ◽  
Michael D. Sunshine ◽  
John J. Greer ◽  
David D Fuller
2012 ◽  
Vol 235 (2) ◽  
pp. 539-552 ◽  
Author(s):  
Charles Nicaise ◽  
Tamara J. Hala ◽  
David M. Frank ◽  
Jessica L. Parker ◽  
Michèle Authelet ◽  
...  

2017 ◽  
Vol 117 (2) ◽  
pp. 767-776 ◽  
Author(s):  
L. M. Mercier ◽  
E. J. Gonzalez-Rothi ◽  
K. A. Streeter ◽  
S. S. Posgai ◽  
A. S. Poirier ◽  
...  

Intraspinal microstimulation (ISMS) using implanted electrodes can evoke locomotor movements after spinal cord injury (SCI) but has not been explored in the context of respiratory motor output. An advantage over epidural and direct muscle stimulation is the potential of ISMS to selectively stimulate components of the spinal respiratory network. The present study tested the hypothesis that medullary respiratory activity could be used to trigger midcervical ISMS and diaphragm motor unit activation in rats with cervical SCI. Studies were conducted after acute (hours) and subacute (5–21 days) C2 hemisection (C2Hx) injury in adult rats. Inspiratory bursting in the genioglossus (tongue) muscle was used to trigger a 250-ms train stimulus (100 Hz, 100–200 μA) to the ventral C4 spinal cord, targeting the phrenic motor nucleus. After both acute and subacute injury, genioglossus EMG activity effectively triggered ISMS and activated diaphragm motor units during the inspiratory phase. The ISMS paradigm also evoked short-term potentiation of spontaneous inspiratory activity in the previously paralyzed hemidiaphragm (i.e., bursting persisting beyond the stimulus period) in ∼70% of the C2Hx animals. We conclude that medullary inspiratory output can be used to trigger cervical ISMS and diaphragm activity after SCI. Further refinement of this method may enable “closed-loop-like” ISMS approaches to sustain ventilation after severe SCI. NEW & NOTEWORTHY We examined the feasibility of using intraspinal microstimulation (ISMS) of the cervical spinal cord to evoke diaphragm activity ipsilateral to acute and subacute hemisection of the upper cervical spinal cord of the rat. This proof-of-concept study demonstrated the efficacy of diaphragm activation, using an upper airway respiratory EMG signal to trigger ISMS at the level of the ipsilesional phrenic nucleus during acute and advanced postinjury intervals.


2021 ◽  
Author(s):  
Teresa Pitts ◽  
Kimberly E Iceman ◽  
Alyssa Huff ◽  
M Nicholas Musselwhite ◽  
Michael L Frazure ◽  
...  

Proper function of the larynx is vital to airway protection, including swallow. While the swallow reflex is controlled by the brainstem, patients with cervical spinal cord injuries (cSCI) are likely at increased risk of disordered swallow (dysphagia) and pneumonia, and the underlying mechanisms are unknown. We aimed to determine if acute spinal cord injury would disrupt swallow function in animal models. We hypothesized that 1) loss of descending efferent information to the diaphragm would affect swallow and breathing differently, and that 2) loss of ascending spinal afferent information would alter central swallow regulation to change motor drive to the upper airway. We recorded amplitudes of laryngeal and inspiratory muscle electromyograms (EMGs), submental and pharyngeal muscle EMGs, and cardiorespiratory measures in freely breathing pentobarbital-anesthetized cats and rats. First, we assessed the effect of a lateral hemisection at the second cervical level (C2) in cats during breathing. Posterior cricoarytenoid (laryngeal abductor) EMG activity during inspiration increased nearly two-fold, indicating that inspiratory laryngeal drive increased following cSCI. Ipsilateral to the injury, the crural diaphragm EMG was significantly reduced during breathing (62 ± 25 percent change post-injury), but no animal had a complete termination of all activity; 75% of animals had an increase in contralateral diaphragm recruitment after cSCI, but this did not reach significance. Next, we assessed the effect of C2 lateral hemisection in cats during swallow. The thyroarytenoid (laryngeal adductor) and thyropharyngeus (pharyngeal constrictor) both increased EMG activity during swallow, indicating increased upper airway drive during swallow following cSCI. There was no change in the number of swallows stimulated per trial. We also found that diaphragm activity during swallow (schluckatmung) was bilaterally suppressed after lateral C2 hemisection, which was unexpected because this injury did not suppress contralateral diaphragm activity during breathing. Swallow-breathing coordination was also affected by cSCI, with more post-injury swallows occurring during early expiration. Finally, because we wanted to determine if the chest wall is a major source of feedback for laryngeal regulation, we performed T1 total transections in rats. As in the cat C2 lateral hemisection, a similar increase in inspiratory laryngeal activity (posterior cricoarytenoid) was the first feature noted after rat T1 complete spinal cord transection. In contrast to the cat C2 lateral hemisection, diaphragmatic respiratory drive increased after T1 transection in every rat (215 ± 63 percent change), and this effect was significant. Overall, we found that spinal cord injury alters laryngeal drive during swallow and breathing, and alters swallow-related diaphragm activity. Our results show behavior-specific effects, suggesting that swallow may be more affected than breathing is by cSCI, and emphasizing the need for additional studies on laryngeal function during breathing and swallow after spinal cord injury.


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