Predictability of Lumbar Spinal Cord Microenvironment after Thoracic Injury based on the Gene Expression Profile of Blood Neutrophils and Monocytes

Abstract

Profound locomotor impairments exist with human spinal cord injury (SCI) even after intensive neuro-rehabilitation. Animal studies show that active recruitment of myeloid cells from the bloodstream into the spinal cord can induce a toxic microenvironment which impedes neuroplasticity and functional recovery. Evidence also shows elevated pro-inflammatory gene expression within infiltrating monocytes in the lumbar cord likely drives inflammation in locomotor networks and impairs recovery. Clinical effective training can only be attained early after SCI and in combination with reduced inflammation. Unfortunately, knowing the real-time microenvironment of the human spinal cord and when it is best to deliver rehabilitation is currently impossible. Therefore, this study aims to predict the lumbar cord microenvironment from gene expression profiles of myeloid cells in blood samples after murine SCI. I hypothesize that changes in gene expression in blood neutrophils and monocytes among four categories–inflammatory, trafficking, extracellular matrix (ECM) remodeling, and growth and repair–will correlate with and predict the lumbar microenvironment. NanoString nCounter technology was used to analyze 60 genes in samples from mice 24 hours after SCI. The expression level of lymphocyte antigen 6 complex (Ly6C) by neutrophils, protein tyrosine phosphatase receptor type C (ptprc/CD45) by monocytes were correlated with expression levels within lumbar cord. Therefore, by measuring their concentration of in blood, we may be closer to being able to predict and assess the microenvironment of lumbar cord in human subjects in a clinically feasible way and to improve the outcome of rehabilitation.A five-year embargo was granted for this item.Academic Major: Neuroscienc

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