Abstract
After spinal cord injury, transected axons fail to regenerate, yet significant, spontaneous functional improvement can be observed over time. Distinct central nervous system regions retain the capacity to generate new neurons and glia from an endogenous pool of progenitor cells and to compensate neural cell loss following certain lesions. The aim of the present study was to investigate whether endogenous cell replacement (neurogenesis or gliogenesis) in the brain (subventricular zone, SVZ; corpus callosum, CC; hippocampus, HC; and motor cortex, MC) or cervical spinal cord might represent a structural correlate for spontaneous locomotor recovery after a thoracic spinal cord injury. Adult Fischer 344 rats received severe contusion injuries (200 kDyn) of the mid-thoracic spinal cord using an Infinite Horizon Impactor. Uninjured rats served as controls. From 4 to 14 days post-injury, both groups received injections of bromodeoxyuridine (BrdU) to label dividing cells. Over the course of six weeks post-injury, spontaneous recovery of locomotor function occurred. Survival of newly generated cells was unaltered in the SVZ, HC, CC, and the MC. Neurogenesis, as determined by identification and quantification of doublecortin immunoreactive neuroblasts or BrdU/neuronal nuclear antigen double positive newly generated neurons, was not present in non-neurogenic regions (MC, CC, and cervical spinal cord) and unaltered in neurogenic regions (dentate gyrus and SVZ) of the brain. The lack of neuronal replacement in the brain and spinal cord after spinal cord injury precludes any relevance for spontaneous recovery of locomotor function. Gliogenesis was increased in the cervical spinal cord remote from the injury site, however, is unlikely to contribute to functional improvement.
Highlights
Spinal cord injury (SCI) with complete axonal transection precludes any degree of sensorimotor or autonomous functional recovery [1,2]
Neurological and consecutively functional recovery is consistently observed in individuals with incomplete SCI, reflected by conversion in the American Spinal Injury Association Impairment Scale and by gains in respective functional assessments, such as the Spinal Cord Independence Measure and the Walking Index for Spinal Cord Injury [3,4,5]
Compared to BBB scores at day 8, locomotor function further improved at day 40, showing spontaneous functional recovery with nearly unimpaired walking patterns (BBB score 11.160.5; p,0.0001; Fig. 1)
Summary
Spinal cord injury (SCI) with complete axonal transection precludes any degree of sensorimotor or autonomous functional recovery [1,2]. Neurological and consecutively functional recovery is consistently observed in individuals with incomplete SCI, reflected by conversion in the American Spinal Injury Association Impairment Scale and by gains in respective functional assessments, such as the Spinal Cord Independence Measure and the Walking Index for Spinal Cord Injury [3,4,5]. The exact structural correlates contributing to functional improvement in incomplete SCI have yet to be determined. It has been shown that axonal sprouting and synaptic rearrangements above and below the injury site in rodent and primate models contribute to recovery of function [6,7,8,9,10]. Whether intrinsic neural cell replacement remote from the injury site underlies the recovery process, at least in part, is yet unknown
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