Neuropathological Characteristics of Brachial Plexus Avulsion Injury With and Without Concomitant Spinal Cord Injury

Abstract

Neonatal brachial plexus avulsion injury (BPAI) commonly occurs as a consequence of birth trauma and can result in lifetime morbidity; however, little is known regarding the evolving neuropathological processes it induces. In particular, mechanical forces during BPAI can concomittantly damage the spinal cord and may contribute to outcome. Here, we describe the functional and neuropathological outcome following BPAI, with or without spinal cord injury, in a novel pediatric animal model. Twenty-eight-day-old piglets underwent unilateral C5–C7 BPAI with and without limited myelotomy. Following avulsion, all animals demonstrated right forelimb monoparesis. Injury extending into the spinal cord conferred greater motor deficit, including long tract signs. Consistent with clinical observations, avulsion with myelotomy resulted in more severe neuropathological changes with greater motor neuron death, progressive axonopathy, and persistent glial activation. These data demonstrate neuropathological features of BPAI associated with poor functional outcome. Interestingly, in contrast to adult small animal models of BPAI, a degree of motor neuron survival was observed, even following severe injury in this neonatal model. If this is also the case in human neonatal BPAI, repair may permit functional restoration. This model also provides a clinically relevant platform for exploring the complex postavulsion neuropathological responses that may inform therapeutic strategies.

Brachial Plexus Anatomy of Miniature Swine Compared to Human

“…The similarities can be appreciated through previous research with swine model post-avulsion injury retaining more similarities to human models in terms of motor neuron death compared to small animal models [30,31]. The differences in physiological responses between these models may be due to species-speci c responses or age differences [5]. The lack of clinically-relevant therapies in rodent models despite their widespread use has resulted in more studies shifting their focus towards larger animal models.…”

“…Injury to C5-C6 nerves causes loss of elbow exion, shoulder abduction, and external rotation. De cits in movements of the ngers and wrist indicate involvement of C7 and C8 spinal nerves [5]. Sensory and motor de cits are accompanied by neuropathic pain in up to 95% of BPIs and can be extremely debilitating [6,7].…”

“…Current treatment methods of BPI include distal nerve transfers, brachial plexus exploration, nerve grafting from residual nerves, free muscle transfers, and tendon transfers [14]. Despite recent advances in nerve repair techniques, the prognosis of BPA, especially panplexus injuries, is generally poor [5,14].…”

Development of a Multimodal Apparatus to Generate Biomechanically Reproducible Spinal Cord Injuries in Large Animals

“…Several types of SCI have been experimented in pigs and may be categorized as follows: (1) compression injuries using clips ( 38 – 40 ) or computer-controlled stepping motor ( 41 ), (2) ischemic injuries with aortic cross or segmental artery occlusion ( 42 – 44 ), (3) root avulsion with ventral myelotomy ( 45 ), (4) vertebral column distraction/retraction ( 46 – 48 ), (5) spinal cord transection/hemisection ( 49 – 51 ), (6) spinal cord contusion using the controlled cortical impactor ( 29 , 37 , 52 ) or a weight-drop impactor ( 18 – 23 ). Despite these studies, there are no commercially available devices adapted to the size and the strength required for a 20–50 kg animal.…”

Comparison of Different In Vivo Animal Models of Brachial Plexus Avulsion and Its Application in Pain Study

“…More precise avulsion of rats' C7 root by Sim et al [ 36 ] and C8 root by Gu et al [ 37 ] was used to evaluate the neuroprotective effect of paclitaxel in the prevention of motoneuron death and mitochondrial dysfunction and to investigate the survival, regeneration, and functional recovery of motor neuron by reimplantation of the ventral root method. Another pediatric pig avulsion model of upper and middle trunks through this approach was used to describe the functional and neuropathological outcome following BPA, with or without spinal cord injury [ 38 ]. Similar rat or mouse models of upper-middle trunk and global trunk avulsion were successively reported to expound the mechanism of motor neuron degeneration and/or to evaluate different repair and reconstruction methods [ 39 – 41 ].…”