No abstract

Spinal cord injury chronically alters cardiac structure and function and is associated with increased odds for cardiovascular disease. Here, we investigate the cardiac consequences of spinal cord injury on the acute-to-chronic continuum, and the contribution of altered bulbospinal sympathetic control to the decline in cardiac function following spinal cord injury. By combining experimental rat models of spinal cord injury with prospective clinical studies, we demonstrate that spinal cord injury causes a rapid and sustained reduction in left ventricular contractile function that precedes structural changes. In rodents, we experimentally demonstrate that this decline in left ventricular contractile function following spinal cord injury is underpinned by interrupted bulbospinal sympathetic control. In humans, we find that activation of the sympathetic circuitry below the level of spinal cord injury causes an immediate increase in systolic function. Our findings highlight the importance for early interventions to mitigate the cardiac functional decline following spinal cord injury.

Interleukin-10 (IL-10) inhibits pro-inflammatory cytokine production in blood leukocytes - an effect mediated by signal transducer and activator of transcription 3 (STAT3) activation. To examine potential sex-based differences in IL-10's anti-inflammatory function, we treated whole blood from healthy males and females (n=16 each; age: 28±6 years; body mass index: 23.5±2.3 kg/m2) with increasing concentrations of IL-10 (1-100 ng/mL) and quantified changes in phosphorylated STAT3 (pSTAT3) in CD14+ monocytes and CD4+ lymphocytes via flow cytometry. In parallel, liposaccharide (LPS)-stimulated whole-blood cultures were used to assess sex-based differences in IL-10's ability to inhibit tumour necrosis factor (TNF)-α production. IL-10 concentration-dependently increased pSTAT3 mean fluorescent intensity (MFI) in CD14+ and CD4+ cells (main effects of concentration, P<0.01) with males exhibiting larger changes in pSTAT3 MFI in both cell types (main effects of sex, P<0.01). Accordingly, IL-10-mediated inhibition of TNF-α production was more pronounced in males (main effect of sex, P<0.01) with changes in other monocyte-derived cytokines (IL-1b, IL-1RA, IL-15) also supporting a sexual dimorphism in IL-10 action (P<0.05). These sex-based differences were not explained by differences in circulating plasma IL-10 concentrations, basal IL-10 receptor expression in unstimulated CD14+ and CD4+ cells, nor the basal expression of IL-10 signaling proteins (STAT3, SHIP1, p38 MAPK) in unstimulated peripheral blood mononuclear cells. We conclude that IL-10's anti-inflammatory function differs between male and female blood leukocytes ex vivo. This sexual dimorphism should be considered in future work investigating IL-10's anti-inflammatory action in humans as it may represent a mechanism contributing to sex differences in overall immune function.

Introduction: Persons with spinal cord injury (SCI) often report high levels of neuropathic pain (NP) and poor well-being, which may result from increased inflammation. This study examined the impact of sub-maximal aerobic exercise on NP, inflammation and psychological affect among adults with SCI.Methods: Eight active adults with tetraplegia (n-4, AIS A-C) and paraplegia (n = 4, AIS A-C) performed 30-min of arm-crank aerobic exercise and reported their ratings of perceived exertion (RPE) each minute. Measures of NP, affect, and inflammatory cytokines (IL-6, IL-10, IL-1ra, TNF-α) were taken pre-(T0), immediately post-(T1), and 90-min post-exercise (T2).Results: NP decreased between T0 and T1 for tetraplegics (−60%, d = 0.47; CI = −0.32, 2.02) and paraplegics (−16%, d = 0.15; CI = −0.30, 0.90). Correlations between change in cytokines and change in NP were medium-to large for tetraplegics (rs ranged from −0.820 to 0.965) and paraplegics (rs ranged from −0.598 to 0.833). However, the pattern of correlations between change in cytokines and affect was inconsistent between groups. Lower baseline levels of IL-1ra predicted greater decreases in NP immediately post-exercise (r = 0.83, p = 0.01).Conclusion: Sub-maximal exercise can positively impact NP for some persons with SCI. Further experimental research should identify the optimal exercise intensity to reduce NP for persons with SCI, in addition to understanding biomarkers which may predict changes in NP.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT03955523.