Accelerated Cardiometabolic Risks and Extant Atherosclerotic Disease in a Model of Spinal Cord Injury
1Bigford G, 2Herderick E, 1Mendez A, 1Nash M
1University of Miami Miller School of Medicine, Miami, FL, USA; 2EEH Science LLC, Pickerington, OH, USA
Objective: to test in a controlled research design whether spinal cord injury (SCI) hastens the native trajectory of, and established component risks for, atherosclerotic disease (AD), and whether Salsalate anti-inflammatory pharmacotherapy will attenuate the impact of SCI.
Design/Methods: 16-week old ApoE-/- mice (C57BL/6 background [B6.129P2ApoEtm1UNC/J]) were anesthetized and underwent a T9 laminectomy. Exposed spinal cords were given a contusion injury (Infinite Horizon) at a force of 70 k-dynes (severe). Sham-operated animals underwent all surgical procedures, excluding injury. SCI animals were randomized to 3 groups: SCI, SCI + Salsalate [120 mg/Kg/day i.p.] for 30-days, and SCI + Vehicle for 30-days. Mice were serially sacrificed at 20-, 24-, and 28-weeks post-SCI. At sacrifice, whole blood was collected via cardiac puncture, centrifuged (5,000 x g, 15 min), and serum stored at -80C. Heart and aorta were harvested intact, fixed in 10% buffered formalin, then stripped of adventitia and cut longitudinally for en face preparation. Total cholesterol (TC) was assayed by enzymatic methods (Roche Diagnostics) and fasting glucose (FG) was determined on an auto-analyzer (Roche Cobas-Mira) using the glucose oxidase method. The aortic tree was stained with oil-red-O (ORO) and AD lesion histomorphometry was calculated from the proportional area of pixels stained with ORO.
Results: TC was significantly higher in SCI mice at 20- and 24-weeks than for ApoE-/- mice alone (control). By 24-weeks, TC in SCI mice + salsalate was significantly lower than SCI. The group mean for FG was higher in SCI mice at 20-weeks than control, although not significantly. However, by 24-weeks, FG was significantly greater in SCI mice compared to control. At 24-weeks, the group mean for FG in SCI + salsalate was lower than SCI, although not significantly. AD lesion area in the aortic arch was greater in SCI than control at 20-weeks, although not statistically significant. Salsalate treatment attenuated the lesion increase in the aortic arch observed with SCI, although lesion area was still greater than control at this early time point. (All significant p’s<0.05).
Conclusions: SCI induced significant increases in component risk factors for AD (TC and FG) and had a direct effect on extant AD, worsening aortic arch atherosclerotic plaques. Salsalate improved SCI-induced effect on TC and FG. These findings show that SCI accelerates AD risk factors and aortic atherosclerotic plaque formation, and that anti-inflammatory treatment may attenuate the impact of SCI on AD outcomes.
Support: This project was funded by the Craig H. Neilsen Foundation, Grant#: 340428
You Must Be Logged In
This Reminders tab will display for your scheduled lectures 15 minutes before start time and for new messages waiting.