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Degeneration and repair after spinal cord injury (SCI) in the non‐human primate (NHP)

We will discuss the establishment of a new NHP model of contusion SCI using an electronically controlled impactor with feedback to produce a unilateral cervical contusion at the C5 vertebral level similar to our rat model. Pre‐op and post‐injury MRIs were taken. Recovery of over‐ground locomotion, climbing and object manipulation were scored in an open‐field; forelimb and sensory function were assessed in a primate chair. EMG activity patterns in forelimb muscles were assessed in one subject. Three subjects had BDA labeling of the cortico‐spinal tract (CST) at 4‐5 months. Peak force during impact was a good predictor of behavioral outcome at 2 weeks (r=0.88; p<0.004). Histological analysis showed that the lesion can be graded, and the injury produces a consistent pattern of degeneration in the gray and white matter, with a central contusion region (that formed a cystic cavity in some animals), with a peripheral rim of spared fibers. At the rim of the contusion, demyelinated axons, remyelinated axons, and macrophages are present. CST tracing shows that this rim can contain spared CST fibers at the lesion epicenter that provide dense innervation of the gray matter below the injury. Microglial activation away from the lesion is prominent in the degenerating tracts. Principle components analysis of the relationships of all injury parameters, behavioral outcomes and histological measures were performed and confirmed that these relationships were consistent with our previous studies in the rat. In addition to providing multiple univariate outcome measures, we also characterized an integrated metric describing the multivariate cervical SCI syndrome. Impacts at the higher ranges of peak force produced highly lateralized and enduring deficits in multiple measures of hind‐limb, fore‐limb and hand function, while lower energy impacts produced early paralysis followed by substantial recovery with enduring deficits in fine digital control (e.g., pincer grasp). (Supported by the VA, CH Neilsen Foundation, and NIH)