Intervertebral disc fluid content increases with treadmill exercise in a rat model

BACKGROUND CONTEXT: The discs are the largest avascular tissues in the body and as a result disc cells that are distant from the vertebral vasculature rely on indirect diffusion and convection of oxygen and glucose from the vertebrae to maintain metabolic processes. Our global hypothesis for this work is that impaired fluid transport (and subsequently nutrient transport) underly the degeneration process and strategies to increase transport may delay or reverse disc degeneration. In previous work, mechanical loading of the spine impacted disc health, where static bending loads induce a degenerative response and dynamic loads in a physiologic range induce an anabolic response. Dynamic loading appears to be important to disc health, as dynamic disc loading causes an increase in small molecule uptake suggesting that the concentration of glucose, a critical nutrient for disc cell metabolism, may be increased with dynamic loading. In these previous studies, discs were loaded using external mechanical loading devices that were surgically affixed to adjacent vertebrae. One way to induce dynamic mechanical loads naturally is through exercise and recent work suggests that exercise is beneficial to the spine and can even reverse surgically-induced disc degeneration. However, the mechanism by which this occurs is not clear. PURPOSE: We hypothesize that exercise improves transport of fluid and nutrients into the intervertebral disc and this drives disc anabolism. In this study, we investigated how disc fluid composition is related to age and disc degeneration in a rat model and determined acute effects of exercise on disc fluid transport. STUDY DESIGN/SETTING: We used magnetic resonance imaging (MRI) to measure how disc fluid composition changes with age as a marker of degeneration and then before and after treadmill walking as a measure of exercise-induced fluid transport. Our hypotheses were that 1) disc fluid decreases with age and 2) disc fluid increases with exercise. PATIENT SAMPLE: Study 1: Effect of age on disc fluid composition Fischer 344 rats from 10-week (n=8, 4M/4F, “young”), 6-9 month (n=8, 4M/4F, “adult”), and 20-month (n=8, 4M/4F, “advanced”) age groups were imaged by MRI and evaluated histologically. Study 2: Effect of exercise on disc fluid composition and glucose uptake 1P0-week Fischer 344 rats (n=8, 4M/4F, “young”) were imaged by MRI before and after treadmill exercise. OUTCOME MEASURES: Disc height and T2 relaxation time. METHODS: Study 1: Effect of age on disc fluid composition. MRI Analysis MRI was performed at 7T (Bruker Avance) using a surface array coil. Rats were anesthetized via isoflurane for the duration of the imaging experiment. Disc geometry was measured in 3D using a sagittal T2 Turbo RARE sequence. Disc boundaries on each slice were manually segmented and compiled in 3D. Mean disc height was calculated as the distance between the centroids of superior and inferior surfaces. Disc fluid composition was measured in a 2D mid-sagittal slice using a T2 mapping sequence. T2 signal intensity at each echo was fit to a single-term exponential decay to calculate T2 relaxation time. Discs were manually segmented, and mean T2 relaxation time was calculated for the whole disc. Histological Analysis Bone-disc-bone segments were isolated from the rat lumbar spine, decalcified, fixed in formalin, and embedded in paraffin. Discs were sectioned at 8 μm, stained with hematoxylin and eosin, and whole-slide brightfield images were captured at 400x. Study 2: Effect of exercise on disc fluid composition and glucose uptake Rats were acclimated to the treadmill over 5 sessions where speed and duration gradually increased to 4 m/min at 60 minutes in the final session. MRI Analysis Rats were imaged by MRI before and after treadmill exercise (4 m/min, 60 min) for disc geometry using a T1 FLASH sequence and for disc fluid composition using a T2 mapping sequence. Between the end of the treadmill walk and the start of the post-exercise T2 map 15±2 min elapsed on average. Statistical Analysis We used linear mixed effects models to account for correlations within individual rats. We evaluated the relationship between age and T2 relaxation time as well as the relationship between exercise and T2 relaxation time, controlling for spinal level. RESULTS: We identified age-related changes in the rat intervertebral disc consistent with mild degeneration. While disc height significantly increased with age (20 months, Δ = 0.1 mm, P=0.009), disc T2 relaxation time significantly decreased (6-9 months: Δ = -9.1 ms, P=0.009; 20 months, Δ = -13.4 ms, P=0.0003). Decreased T2 was apparent in the caudal lumbar levels (L4-L5 to L6-S1) at 6-9 months of age and then across the whole lumbar spine at 20 months. Histological analysis revealed fibrosis of the inner AF and decreased NP size at 20 months, but no apparent changes at 6-9 months. Sixty minutes of treadmill walking caused an increase in disc T2 relaxation time (post-exercise, Δ = 12.1 ms, P=0.03), that was largest in the upper lumbar levels. This change was accompanied by a decrease in disc height of about 5% (post-exercise, Δ = 0.1 mm, P=0.03). CONCLUSIONS: The intervertebral discs degenerate with age and are implicated in low back pain, the world's leading cause of disability. This work suggests that exercise is a natural way to improve transport into the disc and may be beneficial to long-term disc health and prevent low back pain. FDA Device/Drug Status: This abstract does not discuss or include any applicable devices or drugs.

Duke Scholars

Author Stephanie Blocker Radiology