scholarly journals Cardiometabolic risks and atherosclerotic disease in ApoE knockout mice: Effect of spinal cord injury and Salsalate anti-inflammatory pharmacotherapy

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246601
Author(s):  
Gregory E. Bigford ◽  
Angela Szeto ◽  
John Kimball ◽  
Edward E. Herderick ◽  
Armando J. Mendez ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Body Mass ◽  
Atherosclerotic Disease ◽  
Double Mutation ◽  
Monocyte Chemoattractant Protein 1 ◽  
Cord Injury ◽  
Anti Inflammatory ◽  
Associated Risk Factors ◽  
The Impact

Objective To test in mice with a double mutation of the ApoE gene (ApoE-/-) whether spinal cord injury (SCI) hastens the native trajectory of, and established component risks for, atherosclerotic disease (AD), and whether Salsalate anti-inflammatory pharmacotherapy attenuates the impact of SCI. Methods ApoE-/- mice were anesthetized and underwent a T9 laminectomy. Exposed spinal cords were given a contusion injury (70 k-dynes). Sham animals underwent all surgical procedures, excluding injury. Injured animals were randomized to 2 groups: SCI or SCI+Salsalate [120 mg/Kg/day i.p.]. Mice were serially sacrificed at 20-, 24-, and 28-weeks post-SCI, and body mass was recorded. At sacrifice, heart and aorta were harvested intact, fixed in 10% buffered formalin, cleaned and cut longitudinally for en face preparation. The aortic tree was stained with oil-red-O (ORO). AD lesion histomorphometry was calculated from the proportional area of ORO. Plasma total cholesterol, triglycerides and proatherogenic inflammatory cytokines (PAIC’s) were analyzed. Results AD lesion in the aortic arch progressively increased in ApoE-/-, significant at 24- and 28-weeks. AD in SCI is significantly greater at 24- and 28-weeks compared to time-controlled ApoE-/-. Salsalate treatment attenuates the SCI-induced increase at these time points. Body mass in all SCI groups are significantly reduced compared to time-controlled ApoE-/-. Cholesterol and triglycerides are significantly higher with SCI by 24- and 28-weeks, compared to ApoE-/-, and Salsalate reduces the SCI-induced effect on cholesterol. PAIC’s interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-C motif) ligand 5 (CCL-5) are significantly greater with SCI compared to ApoE-/- at varying timepoints. Salsalate confers a marginal reducing effect on PAIC’s by 28-weeks compared to SCI. Regression models determine that each PAIC is a significant and positive predictor of lesion. (p’s <0.05). Conclusions SCI accelerates aortic AD and associated risk factors, and anti-inflammatory treatment may attenuate the impact of SCI on AD outcomes. PAIC’s IL-1β, IL-6, TNFα, MCP-1, and CCL-5 may be effective predictors of AD.

scholarly journals The impact of body mass index on one-year mortality after spinal cord injury

2019 ◽  
pp. 1-9
Author(s):  
Huacong Wen ◽  
Michael J. DeVivo ◽  
Tapan Mehta ◽  
Navneet Kaur Baidwan ◽  
Yuying Chen
Keyword(s):  
Body Mass Index ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Body Mass ◽  
Cord Injury ◽  
One Year ◽  
The Impact

A Pivotal Role of the Nrf2 Signaling Pathway in Spinal Cord Injury: A Prospective Therapeutics Study

2020 ◽  
Vol 19 (3) ◽  
pp. 207-219
Author(s):  
Saeed Samarghandian ◽  
Ali Mohammad Pourbagher-Shahri ◽  
Milad Ashrafizadeh ◽  
Haroon Khan ◽  
Fatemeh Forouzanfar ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
Experimental Studies ◽  
Main Role ◽  
Related Factor ◽  
Nrf2 Signaling Pathway ◽  
Cord Injury ◽  
Anti Inflammatory ◽  
The Impact

The nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway has a main role against oxidative stress and inflammation. Spinal Cord Injury (SCI) leads to the high secretion of inflammatory cytokines and reactive oxygen species, which disturbs nervous system function and regeneration. Several studies have indicated that the activation of the Nrf2 signaling pathway may be effective against inflammation after SCI. The experimental studies have indicated that many chemical and natural agents act as Nrf2 inducer, which inhibits the SCI progression. Thus, the finding of novel Nrf2- inducer anti-inflammatory agents may be a valuable approach in drug discovery. In the present review, we discussed the Nrf2 signal pathway and crosstalk with the NF-&#954;B pathway and also the impact of this pathway on inflammation in animal models of SCI. Furthermore, we discussed the regulation of Nrf2 by several phytochemicals and drugs, as well as their effects on the SCI inhibition. Therefore, the current study presented a new hypothesis of the development of anti-inflammatory agents that mediate the Nrf2 signaling pathway for treating the SCI outcomes.

scholarly journals Spinal Cord Injury Increases Pro-inflammatory Cytokine Expression in Kidney at Acute and Sub-chronic Stages

Inflammation ◽  
2021 ◽  
Author(s):  
Shangrila Parvin ◽  
Clintoria R. Williams ◽  
Simone A. Jarrett ◽  
Sandra M. Garraway
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Inflammatory Cytokine ◽  
Cardiovascular Health ◽  
Mrna Levels ◽  
Post Injury ◽  
Cord Injury ◽  
And Function ◽  
The Impact

Abstract— Accumulating evidence supports that spinal cord injury (SCI) produces robust inflammatory plasticity. We previously showed that the pro-inflammatory cytokine tumor necrosis factor (TNF)α is increased in the spinal cord after SCI. SCI also induces a systemic inflammatory response that can impact peripheral organ functions. The kidney plays an important role in maintaining cardiovascular health. However, SCI-induced inflammatory response in the kidney and the subsequent effect on renal function have not been well characterized. This study investigated the impact of high and low thoracic (T) SCI on C-fos, TNFα, interleukin (IL)-1β, and IL-6 expression in the kidney at acute and sub-chronic timepoints. Adult C57BL/6 mice received a moderate contusion SCI or sham procedures at T4 or T10. Uninjured mice served as naïve controls. mRNA levels of the proinflammatory cytokines IL-1β, IL-6, TNFα, and C-fos, and TNFα and C-fos protein expression were assessed in the kidney and spinal cord 1 day and 14 days post-injury. The mRNA levels of all targets were robustly increased in the kidney and spinal cord, 1 day after both injuries. Whereas IL-6 and TNFα remained elevated in the spinal cord at 14 days after SCI, C-fos, IL-6, and TNFα levels were sustained in the kidney only after T10 SCI. TNFα protein was significantly upregulated in the kidney 1 day after both T4 and T10 SCI. Overall, these results clearly demonstrate that SCI induces robust systemic inflammation that extends to the kidney. Hence, the presence of renal inflammation can substantially impact renal pathophysiology and function after SCI.

scholarly journals Statin use is associated with reduced motor recovery after spinal cord injury

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Erin M. Triplet ◽  
Isobel A. Scarisbrick
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Recovery ◽  
Motor Deficit ◽  
Historical Cohort ◽  
Cholesterol Lowering ◽  
Severity Of Injury ◽  
Cord Injury ◽  
The Impact ◽  
Statin Use

Abstract Study design We completed retrospective analysis of statin use in individuals with neurologically significant spinal cord injury in a historical cohort study. Objective Our objective was to establish the prevalence of cholesterol-lowering agent use following spinal cord injury (SCI) and to determine the impact on recovery of motor function. Setting Patients enrolled in the Rochester Epidemiology Project in Olmsted County, Minnesota, USA from 2005 to 2018 were included in analysis. Methods Exclusion criteria: age <18, comorbid neurological disease, prior neurological deficit, nontraumatic injury, survival <1 year, or lack of motor deficit. Demographics and cholesterol-lowering agent use in 83 individuals meeting all criteria were recorded. A total of 68/83 individuals were then assessed for change in function over the first 2 months after injury using the ISNCSCI motor subscore. Statistical comparison between control and statin groups was done by two-sided Chi-squared test or two-tailed Student’s t test. Generalized regression was performed to assess associations between independent variables and functional outcome. Results 30% of individuals with SCI had a prescription for a cholesterol-lowering agent. No significant differences were observed in severity of injury or demographic composition between groups. The change in motor subscore was reduced in the statin group compared to controls (p = 0.03, Mann–Whitney). Both severity of injury and statin were significant predictors of reduced motor recovery (p = 0.001, and p = 0.04, respectively). Conclusions Both severity of SCI and statins were significant predictors of reduced motor recovery. Additional investigation is needed to address potential impact of statin-therapy in the context of CNS injury and repair.

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