Division of Applied Physiology, Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA.
Brain Behav Immun. 2010 May;24(4):564-8. doi: 10.1016/j.bbi.2009.12.011. Epub 2010 Jan 4.
Fatigue associated with recovery from muscle damage has recently been linked to increases in brain and muscle proinflammatory cytokines. However, little is known regarding the origin of these cytokines. Since macrophage-like cells in the brain are a primary source of cytokines, we used a brain specific macrophage depletion technique involving liposome encapsulated clodronate (CLD) to examine the role of macrophages on brain IL-1beta and fatigue following eccentric exercise-induced muscle damage. Mice were assigned to six groups: Downhill saline (DWNSAL), downhill clodronate (DWNCLD), uphill saline (UPSAL), uphill clodronate (UPCLD), non-running saline (CONSAL) or non-running clodronate (CONCLD). Mice were given intracerebroventricular (ICV) (10 microL) injections of clodronate-filled liposomes (CLD) to deplete macrophages, or saline-filled liposomes (SAL) and run on a treadmill at 22m/min and -14% (DWN) or 14% (UP) grade for 150 min. A subset of uphill and downhill running mice (n=40) was then run to fatigue on a treadmill at 36m/min, 8% grade at 24h after the uphill and downhill runs. A second subset of uphill, downhill, and control mice (n=30) was sacrificed 24h after the run for analysis of brain IL-1beta concentration. Histological examination confirmed previous reports that CLD administration reduced perivascular and meningeal macrophage subsets in the brain. CLD reduced IL-1beta concentration in the cortex of DWN mice (P<0.05), which was associated with enhanced treadmill performance 24h after both uphill and downhill runs (P<0.05) although the magnitude was greater following the downhill run. These results suggest that brain macrophages can contribute to the increase in brain IL-1beta and fatigue that are associated with recovery from exercise-induced muscle damage.
与肌肉损伤恢复相关的疲劳最近与大脑和肌肉促炎细胞因子的增加有关。然而，对于这些细胞因子的来源知之甚少。由于大脑中的巨噬细胞样细胞是细胞因子的主要来源，我们使用了一种涉及脂质体包裹的氯膦酸（CLD）的大脑特异性巨噬细胞耗竭技术，以研究巨噬细胞在离心运动引起的肌肉损伤后大脑 IL-1beta 和疲劳中的作用。将小鼠分为六组：下坡生理盐水（DWNSAL）、下坡氯膦酸（DWNCLD）、上坡生理盐水（UPSAL）、上坡氯膦酸（UPCLD）、非跑步生理盐水（CONSAL）或非跑步氯膦酸（CONCLD）。通过脑室内（ICV）（10μL）注射 CLD 填充的脂质体（CLD）或 SAL 填充的脂质体（SAL）来耗尽巨噬细胞，然后让小鼠在跑步机上以 22m/min 和-14%（DWN）或 14%（UP）坡度跑步 150 分钟。然后，一部分上坡和下坡跑步的小鼠（n=40）在 24 小时后以 36m/min、8%坡度的跑步机上跑步至疲劳。另一部分上坡、下坡和对照小鼠（n=30）在跑步后 24 小时处死，用于分析大脑 IL-1beta 浓度。组织学检查证实了之前的报道，即 CLD 给药减少了大脑中的血管周围和脑膜巨噬细胞亚群。CLD 降低了 DWN 小鼠大脑皮层中的 IL-1beta 浓度（P<0.05），这与跑步后 24 小时上坡和下坡跑步时跑步机性能的提高有关（P<0.05），尽管下坡跑步后的幅度更大。这些结果表明，大脑巨噬细胞可能导致与运动引起的肌肉损伤恢复相关的大脑 IL-1beta 和疲劳增加。
