The propriospinal system is important in mediating reflex control and in coordination during locomotion. Propriospinal neurons (PNs) present varied patterns of projections with ascending and/or descending fibers. Following spinal cord contusion injury (SCI) in the rat, certain supraspinal pathways, such as the corticospinal tract, appear to be completely abolished, whereas others, such as the rubrospinal and vestibuospinal tracts, are only partially damaged. The amount of damage to propriospinal axons following different severities of SCI is not fully known. In the present study retrograde and anterograde tracing techniques were used to assess the projection patterns of propriospinal neurons in order to determine how this system is affected following SCI. Our findings reveal that PNs have differential vulnerabilities to SCI. While short thoracic propriospinal axons are severely damaged after injury, 5-7% of long descending propriospinal tract (LDPT) projections survive following 50 and 12.5-mm weight drop contusion lesions, respectively, albeit with a reduced intensity of retrograde label. Even though the axons of short thoracic propriospinal cells are damaged, their cell bodies of origin remain intact 2 weeks after injury, indicating that they have not undergone postaxotomy retrograde cell death at this time point. Thus, short PNs may constitute a very attractive population of cells to study regenerative approaches, whereas LDPT neurons with spared axons could be targeted with therapeutic interventions, seeking to enhance recovery of function following incomplete lesions to the spinal cord.
Study design: In vivo study using a moderate spinal cord contusion injury (SCI) model in adult rat. Objective: To assess the immunomodulatory effects of the purine nucleoside inosine on macrophage/ microglia activation at and near the lesion site and in white matter areas remote from the injury epicenter. Setting: Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY, USA. Methods: Animals (N ¼ 56) were injured using a moderate SCI at T9-T10 spinal level and were divided into three groups, depending on treatment paradigm. Rats received either intraperitoneal or subcutaneous injections of inosine (N ¼ 28) or vehicle (N ¼ 28). Spinal cord tissue was processed for ED-1 immunoreactivity and the volume fraction of ED-1 þ profiles was calculated using the Cavalieri method and unbiased stereology. Results: The volume fraction of ED-1 þ profiles within gray and lateral white matter regions at and around the lesion site was significantly reduced only following a twice daily-6 week treatment course, compared with vehicle controls, and white matter areas remote from the lesion were unaffected by all inosine treatment paradigms. Conclusions: Continued subcutaneous delivery of inosine, beginning 15-min post-SCI and persisting throughout the survival period of 6 weeks exerted immunomodulatory effects at and around the lesion site.
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