title: Role of brain macrophages on IL-1beta and fatigue following eccentric exercise-induced muscle damage.
abstract: 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.
authors.affiliation: Division of Applied Physiology, Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Carmichael
authors.forename: J Mark
authors.initials: JM
authors.lastname: Davis
authors.forename: E Angela
authors.initials: EA
authors.lastname: Murphy
authors.forename: James A
authors.initials: JA
authors.lastname: Carson
authors.forename: N
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: Eugene
authors.initials: E
authors.lastname: Mayer
authors.forename: Abdul
authors.initials: A
authors.lastname: Ghaffar
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D007276:Injections, Intraventricular; D053583:Interleukin-1beta / Q000378:metabolism*; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008578:Meninges / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018763:Muscle Fatigue; D018482:Muscle, Skeletal / Q000293:injuries* / Q000503:physiopathology; D010805:Physical Conditioning, Animal / Q000379:methods; D020127:Recovery of Function; D012420:Running; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D053583:Interleukin-1beta; D008081:Liposomes; D004002:Clodronic Acid