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

Satzer D, Miller C, Maxon J, Voth J, DiBartolomeo C, Mahoney R, Dutton JR, Low WC, Parr AM - BMC Neurosci (2015)

Bottom Line: 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.Immunostaining for macrophage markers revealed no T cell-dependent difference in the acute macrophage infiltrate.T cell inhibition combined with other neuroprotective treatment may thus be a promising therapeutic avenue.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, University of Minnesota, D429 Mayo Memorial Building, MMC 96, 420 Delaware Street, SE, Minneapolis, MN, 55455, USA. satz0002@umn.edu.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Expression ranges for individual tissue samples. Box-and-whisker plot of log(FPKM) for each animal (3-digit identification number). Whiskers indicate 1st to 99th percentile; values outside this range are not represented. Note that the expression ranges were highly consistent between samples
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Fig2: Expression ranges for individual tissue samples. Box-and-whisker plot of log(FPKM) for each animal (3-digit identification number). Whiskers indicate 1st to 99th percentile; values outside this range are not represented. Note that the expression ranges were highly consistent between samples

Mentions: RNA samples sent for sequencing had 1.8–10 ng of RNA at a concentration of 92–100 ng/µL and an RNA integrity number (RIN) of 9.7–10. For each sample, 40.0–51.6 million reads 51 base pairs in length were sequenced. Both paired read sets for every sample had a per-base first-quartile Phred quality score greater than 30 for all bases, indicating a base measurement error less than 0.1 %. Expression ranges were highly consistent between samples (Fig. 2).Fig. 2


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

Satzer D, Miller C, Maxon J, Voth J, DiBartolomeo C, Mahoney R, Dutton JR, Low WC, Parr AM - BMC Neurosci (2015)

Expression ranges for individual tissue samples. Box-and-whisker plot of log(FPKM) for each animal (3-digit identification number). Whiskers indicate 1st to 99th percentile; values outside this range are not represented. Note that the expression ranges were highly consistent between samples
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4635574&req=5

Fig2: Expression ranges for individual tissue samples. Box-and-whisker plot of log(FPKM) for each animal (3-digit identification number). Whiskers indicate 1st to 99th percentile; values outside this range are not represented. Note that the expression ranges were highly consistent between samples
Mentions: RNA samples sent for sequencing had 1.8–10 ng of RNA at a concentration of 92–100 ng/µL and an RNA integrity number (RIN) of 9.7–10. For each sample, 40.0–51.6 million reads 51 base pairs in length were sequenced. Both paired read sets for every sample had a per-base first-quartile Phred quality score greater than 30 for all bases, indicating a base measurement error less than 0.1 %. Expression ranges were highly consistent between samples (Fig. 2).Fig. 2

Bottom Line: 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.Immunostaining for macrophage markers revealed no T cell-dependent difference in the acute macrophage infiltrate.T cell inhibition combined with other neuroprotective treatment may thus be a promising therapeutic avenue.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, University of Minnesota, D429 Mayo Memorial Building, MMC 96, 420 Delaware Street, SE, Minneapolis, MN, 55455, USA. satz0002@umn.edu.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus