T cell deficiency in spinal cord injury: altered locomotor recovery and whole-genome transcriptional analysis
| Autor: | Jacob R. Maxon, David Satzer, James R. Dutton, Christina DiBartolomeo, Joseph P. Voth, Rebecca Mahoney, Ann M. Parr, Walter C. Low, Catherine Miller |
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| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
T-Lymphocytes T cell Gene Expression Inflammation Spinal cord injury Biology Neuroprotection Locomotor function Rats Sprague-Dawley Rats Nude Cellular and Molecular Neuroscience Immune system Internal medicine medicine Animals Cytotoxic T cell Macrophage Spinal Cord Injuries Neurons Behavior Animal Cell Death General Neuroscience Recovery of Function medicine.disease T cell deficiency Rats Neuronal cell death Disease Models Animal medicine.anatomical_structure Endocrinology Female medicine.symptom Axonal regeneration Neuroscience Locomotion Research Article |
| Zdroj: | BMC Neuroscience |
| ISSN: | 1471-2202 |
| DOI: | 10.1186/s12868-015-0212-0 |
| Popis: | Background T 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. Methods In 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. Results Athymic 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. Conclusions We 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. Electronic supplementary material The online version of this article (doi:10.1186/s12868-015-0212-0) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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