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PhD Candidate, Florida State University

PINBOARD SUMMARY

The Role of Bone Marrow Derived Macrophages in Spinal Cord Injury

In the United States alone, there are an estimated 17,000 new spinal cord injury cases each year. Even with timely medical interventions, the primary injury is often exacerbated by a period of inflammation and pathological vascular changes that result in additional secondary injuries. During both the primary and secondary injuries, substantial quantities of myelin debris is generated from dying glia and neurons. While it is known that myelin debris clearance by professional phagocytes such as macrophages is a prerequisite for inflammation resolution, it is unclear how to mitigate the deleterious effects that accompany an increased macrophage presence in the lesion. We previously demonstrated that bone marrow derived macrophages (BMDM). but not resident microglia, are the primary phagocytes in the injured spinal cord. Following recruitment from the blood, BMDM are retained in the lesion epicenter for protracted periods of time where they engulf myelin debris and become myelin laden macrophages which contribute to the secondary injury. We have also found that exposure to myelin debris supports long-term BMDM survival, prolonging their potential to induce damage. Thus, the therapeutic manipulation of infiltrating BMDM represents a means to limit secondary injuries and promote functional recovery

4 ITEMS PINNED

Nogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology.

Abstract: Two hallmarks of chronic multiple sclerosis lesions are the absence of significant spontaneous remyelination and primary as well as secondary neurodegeneration. Both characteristics may be influenced by the presence of inhibitory factors preventing myelin and neuronal repair. We investigated the potential of antibodies against Nogo-A, a well-known inhibitory protein for neuronal growth and plasticity, to enhance neuronal regeneration and remyelination in two animal models of multiple sclerosis. We induced a targeted experimental autoimmune encephalomyelitis (EAE) lesion in the dorsal funiculus of the cervical spinal cord of adult rats resulting in a large drop of skilled forelimb motor functions. We subsequently observed improved recovery of forelimb function after anti-Nogo-A treatment. Anterograde tracing of the corticospinal tract revealed enhanced axonal sprouting and arborisation within the spinal cord gray matter preferentially targeting pre-motor and motor spinal cord laminae on lesion level and above in the anti-Nogo-A-treated animals. An important additional effect of Nogo-A-neutralization was enhanced remyelination observed after lysolecithin-induced demyelination of spinal tracts. Whereas remyelinated fiber numbers in the lesion site were increased several fold, no effect of Nogo-A-inhibition was observed on oligodendrocyte precursor proliferation, migration, or differentiation. Enhancing remyelination and promoting axonal regeneration and plasticity represent important unmet medical needs in multiple sclerosis. Anti-Nogo-A antibodies hold promise as a potential new therapy for multiple sclerosis, in particular during the chronic phase of the disease when neurodegeneration and remyelination failure determine disability evolution.

Pub.: 25 Jun '17, Pinned: 28 Jun '17

Longitudinal prediction of quality of life scores and locomotion in individuals with traumatic spinal cord injury.

Abstract: The study examined differences in quality of life scores for groups based on transitions in locomotion status at 1, 5, and 10 years post-discharge in a sample of people with spinal cord injury (SCI). We also investigated whether demographic factors and transitions in locomotion status can predict quality of life measures at these time points.Retrospective case study of the National SCI Database.Model SCI Systems Centers.10,190 individuals with SCI from 21 SCI Model Systems Centers, identified through the National SCI Model Systems Centers database between the years 1985-2012. Subjects had Functional Independence Measure (Locomotion-Mode) data at discharge and at least one of the following: 1, 5, or 10 years post-discharge.Not applicable.Functional Independence Measure - Locomotion Mode; Severity of Depression Scale; Satisfaction with Life scale; Craig Handicap Assessment and Reporting Technique.Participants who transitioned from ambulation to wheelchair use reported lower participation and life satisfaction, and higher depression levels (p<.05) than those who maintained their ambulatory status. Participants who transitioned from ambulation to wheelchair use reported higher depression levels (p<.05) and no difference for participation (p>.05) or life satisfaction (p>.05) compared to those who transitioned from wheelchair to ambulation. Demographic factors and locomotion transitions predicted quality of life scores at all time points (p<.05).The results of this study indicate that transitioning from ambulation to wheelchair use can negatively impact psychosocial health 10 years after SCI. Clinicians should be aware of this when deciding on ambulation training. Further work to characterize who may be at risk for these transitions is needed.

Pub.: 26 Jun '17, Pinned: 28 Jun '17