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Ischemia‐reperfusion modulates the inflammatory and regenerative response to muscle contusion injury
Author(s) -
Ghaly Ahmed,
Marsh Daniel R
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a872-c
Subject(s) - medicine , fibrosis , skeletal muscle , ischemia , inflammation , oxidative stress , cd68 , regeneration (biology) , pathology , myeloperoxidase , reperfusion injury , tibialis anterior muscle , immunohistochemistry , biology , microbiology and biotechnology
Numerous coordinated events must occur for complete regeneration of skeletal muscle following injury. When regeneration is incomplete, muscle is replaced by fibrotic scar tissue. It is our hypothesis that the inflammatory response normally facilitates muscle regeneration, but can be modulated by oxidative stress to exacerbate fibrosis. In this study, we used ischemia and reperfusion (I‐R) to generate oxidative stress and modulate inflammation and fibrosis after skeletal muscle injury. Male F344/BN rats, aged 2 months, were assigned to one of four groups: (1) Uninjured control, (2) Clip compression (200g) of the tibialis anterior (TA) muscle, (3) Femoral artery and vein occluded for two hours, causing I‐R insult, (4) Clip compression of the TA, two hours after I‐R. The relative levels of GP91 phox (oxidative species marker), MPO (neutrophil marker), CINC‐1 (neutrophil chemoattractant), and CD68 (macrophage marker) were quantitated at 8 and 72h post‐injury. Clip‐injured I‐R muscle had elevated GP91 phox (304 ± 70%) when compared to I‐R (102 ± 66%) or injured muscle alone (122 ± 22%). At 8 hours, MPO activity and CINC‐1 levels were elevated in both ischemic (1.83 ± 0.14 U/mg and 85.4 ± 20.5 pg/mg, respectively) and non‐ischemic (1.58 ± 0.40 U/mg and 86.5 ± 13.2 pg/mg) clip‐injured muscle compared to controls (0.12 ± 0.05 U/mg and 1.8 ± 0.1 pg/mg). By 3 days, MPO levels decreased, but remained elevated in the clip‐injured I‐R muscle (1.22 ± 0.10 U/mg) compared to clip‐injury alone (0.65 ± 0.13 U/mg). At 21 days post‐injury, increased collagen deposition and fibrotic tissue were observed in clip‐injured muscle preceded by I‐R. We conclude that oxidative stress modulates the inflammatory response, inhibiting regeneration and exacerbating fibrosis. (Supported by NSERC and NSHRF)