T cell deficiency in spinal cord injury: altered locomotor recovery and whole-genome transcriptional analysis

BMC Neuroscience

Research Article

Christina DiBartolomeo¹  Jacob Maxon¹  Catherine Miller¹  David Satzer¹  Ann M. Parr²  Walter C. Low²  Rebecca Mahoney³  James R. Dutton³  Joseph Voth³ 

[1] Department of Neurosurgery, University of Minnesota, D429 Mayo Memorial Building, MMC 96, 420 Delaware Street, SE, 55455, Minneapolis, MN, USA;Department of Neurosurgery, University of Minnesota, D429 Mayo Memorial Building, MMC 96, 420 Delaware Street, SE, 55455, Minneapolis, MN, USA;Stem Cell Institute, University of Minnesota, 55455, Minneapolis, MN, USA;Stem Cell Institute, University of Minnesota, 55455, Minneapolis, MN, USA;

关键词: Spinal cord injury;    Inflammation;    Locomotor function;    Neuronal cell death;    Axonal regeneration;   

DOI  :  10.1186/s12868-015-0212-0

 received in 2015-02-24, accepted in 2015-10-23,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundT cells undergo autoimmunization following spinal cord injury (SCI) and play both protective and destructive roles during the recovery process. T cell-deficient athymic nude (AN) rats exhibit improved functional recovery when compared to immunocompetent Sprague–Dawley (SD) rats following spinal cord transection.MethodsIn the present study, we evaluated locomotor recovery in SD and AN rats following moderate spinal cord contusion. To explain variable locomotor outcome, we assessed whole-genome expression using RNA sequencing, in the acute (1 week post-injury) and chronic (8 weeks post-injury) phases of recovery.ResultsAthymic nude rats demonstrated greater locomotor function than SD rats only at 1 week post-injury, coinciding with peak T cell infiltration in immunocompetent rats. Genetic markers for T cells and helper T cells were acutely enriched in SD rats, while AN rats expressed genes for Th2 cells, cytotoxic T cells, NK cells, mast cells, IL-1a, and IL-6 at higher levels. Acute enrichment of cell death-related genes suggested that SD rats undergo secondary tissue damage from T cells. Additionally, SD rats exhibited increased acute expression of voltage-gated potassium (Kv) channel-related genes. However, AN rats demonstrated greater chronic expression of cell death-associated genes and less expression of axon-related genes. Immunostaining for macrophage markers revealed no T cell-dependent difference in the acute macrophage infiltrate.ConclusionsWe put forth a model in which T cells facilitate early tissue damage, demyelination, and Kv channel dysregulation in SD rats following contusion SCI. However, compensatory features of the immune response in AN rats cause delayed tissue death and limit long-term recovery. T cell inhibition combined with other neuroprotective treatment may thus be a promising therapeutic avenue.

【 授权许可】

CC BY   
© Satzer et al. 2015