There are currently about 85 000 Canadians living with spinal cord injuries, more than half of which are secondary to trauma.1 As the population ages, the incidence and prevalence of traumatic spinal cord injury are expected to increase, primarily as a result of fall-related injuries among older adults 2 . Therefore, treating spinal cord injuries is relevant not only to spine surgeons and physiatrists, but also to the general clinician who will increasingly encounter such patients in the emergency department or family practice.Here, we review relevant pathophysiology and recent evidence pertaining to the medical, surgical and cellular-based treatment of acute traumatic spinal cord injury. Most of the identified pharmacologic studies were randomized trials or early phase nonrandomized pro spective studies. Research relating to the remaining topics was predominately observational in design (Box 1).

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The mechanisms by which neural precursor cells (NPCs) enhance functional recovery from spinal cord injury (SCI) remain unclear. Spinal cord injured rats were transplanted with wild-type mouse NPCs, shiverer NPCs unable to produce myelin, dead NPCs, or media. Most animals also received minocycline, cyclosporine, and perilesional infusion of trophins. Motor function was graded according to the BBB scale. H&E/LFB staining was used to assess gray and white matter, cyst, and lesional tissue. Mature oligodendrocytes and ED1 + inflammatory cells were quantitated. Confocal and electron microscopy were used to assess the relationship between the transplanted cells and axons. Pharmacotherapy and trophin infusion preserved gray matter, white matter, and oligodendrocytes. Trophin infusion also significantly increased cyst and lesional tissue volume as well as inflammatory infiltrate, and functional recovery was reduced. Animals transplanted with wild-type NPCs showed greatest functional recovery; animals transplanted with shiverer NPCs performed the worst. Wild-type NPCs remyelinated host axons. Shiverer NPCs ensheathed axons but did not produce MBP. These results suggest that remyelination by NPCs is an important contribution to functional recovery following SCI. Shiverer NPCs may prevent remyelination by endogenous cells capable of myelin formation. These findings suggest that remyelination is an important therapeutic target following SCI.

Human male infertility affects w5% of men, with one-third suffering from testicular failure, likely the result of an underlying genetic abnormality that disrupts spermatogenesis during development. Mouse models of male infertility such as the Ppp1cc knockout mouse display very similar phenotypes to humans with testicular failure. Male Ppp1cc mutant mice are sterile due to disruptions in spermatogenesis that begin during prepubertal testicular development, and continue into adulthood, often resulting in loss of germ cells to the point of Sertoli cell-only syndrome. The current study employs light and electron microscopy to identify new morphological abnormalities in Ppp1cc mutant seminiferous epithelium. This study reveals that germ cells become delayed in their development around stages VII and VIII of spermatogenesis. Loss of these cells likely results in the reduced numbers of elongating spermatids and spermatozoa previously observed in mutant animals. Interestingly, Ppp1cc mutants also display reduced numbers of spermatogonia compared with their wild-type counterparts. Using electron microscopy, we have shown that junction complexes in Ppp1cc mutants are ultrastructurally normal, and therefore do not contribute to the breakdown in tissue architecture seen in mutants. Electron microscopy revealed major acrosomal and chromatin condensation defects in Ppp1cc mutants. Our observations are discussed in the context of known molecular changes in Ppp1cc mutant testes.

Despite the increasing incidence and prevalence of cervical spinal cord injury (cSCI), we lack clinically relevant animal models that can be used to study the pathomechanisms of this injury and test new therapies. Here, we characterize a moderate cervical contusion-compression model in rats that is similar to incomplete traumatic cSCI in humans. We characterized the effects of 18-g clip-compression injury at cervical level C6 over an 8-week recovery period. Using Luxol fast blue/hematoxylin-eosin staining in combination with quantitative stereology, we determined that 18-g injury results in loss of gray matter (GM), white matter (WM), as well as in cavity formation. Magnetization transfer and T2-weighted magnetic resonance imaging were used to analyze lesion dynamics in vivo. This analysis demonstrated that both techniques are able to differentiate between the injury epicenter, subpial rim, and WM distal to the injury. Neurobehavioral assessment of locomotor function using Basso, Beattie, and Bresnahan (BBB) scoring and CatWalk revealed limited recovery from clip-compression injury at C6. Testing of forelimb function using grip strength demonstrated significant forelimb dysfunction, similar to the loss of upper-limb motor function observed in human cSCI. Sensory-evoked potentials recorded from the forelimb and Hoffman reflex recorded from the hindlimb confirmed the fore-and hindlimb deficits observed in our neurobehavioral analysis. Here, we have characterized a clip-compression model of incomplete cSCI that closely models this condition in humans. This work directly addresses the current lack of clinically relevant models of cSCI and will thus contribute to improved success in the translation of putative therapies into the clinic.