Secondary Damage in the Spinal Cord after Motor Cortex Injury in Rats

Abstract

When neurons within the motor cortex are fatally injured, their axons, many of which project into the spinal cord, undergo wallerian degeneration. Pathological processes occurring downstream of the cortical damage have not been extensively studied. We created a focal forelimb motor cortex injury in rats and found that axons from cell bodies located in the hindlimb motor cortex (spared by the cortical injury) become secondarily damaged in the spinal cord. To assess axonal degeneration in the spinal cord, we quantified silver staining in the corticospinal tract (CST) at 1 week and 4 weeks after the injury. We found a significant increase in silver deposition at the thoracic spinal cord level at 4 weeks compared to 1 week post-injury. At both time points, no degenerating neurons could be found in the hindlimb motor cortex. In a separate experiment, we showed that direct injury of neurons within the hindlimb motor cortex caused marked silver deposition in the thoracic CST at 1 week post-injury, and declined thereafter. Therefore, delayed axonal degeneration in the thoracic spinal cord after a focal forelimb motor cortex injury is indicative of secondary damage at the spinal cord level. Furthermore, immunolabeling of spinal cord sections showed that a local inflammatory response dominated by partially activated Iba-1-positive microglia is mounted in the CST, a viable mechanism to cause the observed secondary degeneration of fibers. In conclusion, we demonstrate that following motor cortex injury, wallerian degeneration of axons in the spinal cord leads to secondary damage, which is likely mediated by inflammatory processes.

Ex Vivo Diffusion Tensor Imaging of Spinal Cord Injury in Rats of Varying Degrees of Severity

“…30 In general, there is strong evidence of changes in the number of inflammatory cells at locations away from the injury site and even outside of the spinal cord. [31][32][33][34][35] The activation of the inflammatory processes helps to explain the FIG. 6.…”

Neurotrophin‐3 released from implant of tissue‐engineered fibroin scaffolds inhibits inflammation, enhances nerve fiber regeneration, and improves motor function in canine spinal cord injury

“…A local immune reaction in the spinal cord following injury is elicited in rats24 and monkeys 25. The ensuing recruitment of inflammatory cells dominates the resources in the injury site of spinal cord rostral and caudal to the epicenter, and this can lead to progressive degeneration of neurons 26.…”

Severity of spinal cord injury influences diffusion tensor imaging of the brain

“…8 Ten weeks has also been used as a time point by other groups. 18,21 At 10 weeks, the initial acute and inflammatory responses have passed; however, inflammatory cells have been found at locations away from the injury site [22][23][24][25] into regions as far from the injury as the brain. 26 These changes appear to accompany the progression of axonal degeneration and likely reflect the underlying structural changes in tissue associated with the histopathological processes that occur after SCI.…”

“…16 Similar changes occur in the opposite direction; cytotoxic inflammation resulting from damage to the motor cortex extends down through the spinal cord in connected axons. 25 Additional tissue structural changes occur as the system recovers. Following a thoracic lesion in the rat, sprouting of descending fibers from the midbrain occurs.…”