Mora, Juan Carlos García

Respiratory failure is one of the most important complications of cervical spinal cord injury. The level of injury critically determines the severity of the complications. We hypothesized that higher cervical contusion injuries will compromise the motor neuron pool and the descending bulbospinal projections, causing greater functional compromise than contusions at lower levels. Unilateral contusion was performed on adult rats at either the C3 or C5 levels vs. laminectomy. No deficit was seen in ventilatory and non‐ventilatory behaviors as assessed by whole body plethysmography or chronic diaphragm electromyography up to 2 weeks. Contusion injuries at either level resulted in similarly sized cavity formation. Phrenic motor neuron loss differed, with C3 contusion causing a 50% loss of phrenic motor neurons, and C5 contusion only 20% loss compared to the contralateral side. The percent of NMJs that were denervated followed a segmental pattern. Following C3 contusion, ventral regions of the diaphragm displayed denervation of ~30% of NMJs compared to 1‐3% in the C5 contusion and laminectomy groups. In contrast, following C5 contusion, denervation was evident only in dorsal regions (~10%). These results show minimal ventilatory impairment following contusion injuries to the mid‐cervical spinal cord that result in phrenic motor neuron loss and evidence of diaphragm muscle denervation. Grant Funding Source : Supported by NIH grant R01 HL096750 and the Mayo Clinic

Midcervical contusion injuries disrupt descending ipsilateral excitatory bulbospinal projections to phrenic motoneurons, compromising ventilation. We hypothesized that a unilateral contusion injury at C3 versus C5 would differentially impact phrenic activity reflecting more prominent disruption of ipsilateral descending excitatory drive to more caudal segments of the phrenic motor pool with more cranial injuries. Phrenic motoneuron counts and evidence of diaphragm muscle denervation at individual neuromuscular junctions (NMJ) were evaluated at 14 days post-injury after unilateral contusion injury (100 kDynes). Whole body plethysmography and chronic diaphragm EMG were measured before the injury and at 3, 7, and 14 days post-injury. Contusion injuries at either level resulted in a similarly sized cavity. C3 contusion resulted in loss of 39 ± 13% of ipsilateral phrenic motoneurons compared with 13 ± 21% after C5 contusion ( p = 0.003). Cervical contusion injuries resulted in diaphragm muscle denervation (C3 contusion: 17 ± 4%; C5 contusion: 7 ± 4%; p = 0.047). The pattern of denervation revealed segmental innervation of the diaphragm muscle, with greater denervation ventrally after C3 contusion and dorsally after C5 contusion. Overall, diaphragm root mean square electromyography activity did not change ipsilaterally after C3 or C5 contusion, but increased contralaterally (∼11%) after C3 contusion only on the first day post-injury ( p = 0.026). Similarly, there were no significant changes in breathing parameters during eupnea or exposure to hypoxia (10% O 2 ) – hypercapnia (5% CO 2 ) at any time post-injury. Unilateral midcervical contusions minimally impair ventilatory behaviors despite phrenic motoneuron loss and diaphragm muscle denervation.