{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T15:32:06Z","timestamp":1772551926827,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Muscles"],"abstract":"<jats:p>Peripheral arterial disease is a leading cause of amputation and\/or death worldwide. Phosphodiesterase 4 (PDE 4) inhibitors demonstrated beneficial effects in ischemia\u2013reperfusion (IR) settings, but whether PDE 4 inhibition protects skeletal muscle against IR deleterious effects is unknown. We therefore performed limb IR (two hours each) in twenty-one male Swiss mice (12\u201316-week-old) treated or not with Rolipram (1 mg\/kg i.p. 30 min before ischemia and 5 min before reperfusion). The muscles were analyzed 4 h after the onset of ischemia. IR significantly increased leucocyte infiltration (93.13 \u00b1 6.886 vs. 150.1 \u00b1 18.38 cells\/mg of muscle, p &lt; 0.05) and apoptosis (Bax\/Bcl2 ratio, +239%, p &lt; 0.05), together with enhanced mitochondrial fission transcripts (+224% for Drp1, p &lt; 0.01 and +368%, p &lt; 0.0001 for Fis1), and decreased mitochondrial respiration and antioxidant defense. PDE 4 inhibition reduced leucocyte infiltration (150.1 \u00b1 18.38 vs. 55.58 \u00b1 13.83; p &lt; 0.01) and apoptosis (+67%, NS) in association with reduced fission markers (+91% for Drp 1 and +111%, p &lt; 0.05, for Fis 1). Muscle mitochondrial respiration did not improve. In conclusion, PDE 4 inhibition using Rolipram partly protected skeletal muscles against IR-induced deleterious effects. These data support further studies investigating the usefulness of leucocytes modulation in lower-limb IR and a potential beneficial effect of PDE 4 inhibition in peripheral arterial disease.<\/jats:p>","DOI":"10.3390\/muscles5010019","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T09:45:12Z","timestamp":1772531112000},"page":"19","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phosphodiesterase 4 (PDE 4) Inhibition Reduces Ischemia\u2013Reperfusion-Induced Leucocyte Infiltration, Apoptosis and Mitochondrial Fission Markers in Mice Skeletal Muscles Four Hours After Ischemia Onset"],"prefix":"10.3390","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3557-2642","authenticated-orcid":false,"given":"Anne-Laure","family":"Charles","sequence":"first","affiliation":[{"name":"UR 3072, \u201cMitochondria, Oxidative Stress and Muscle Plasticity\u201d, Biomedicine Research Center of Strasbourg (CRBS), Faculty of Medicine, University of Strasbourg, 67081 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliane","family":"Tetsi","sequence":"additional","affiliation":[{"name":"UR 3072, \u201cMitochondria, Oxidative Stress and Muscle Plasticity\u201d, Biomedicine Research Center of Strasbourg (CRBS), Faculty of Medicine, University of Strasbourg, 67081 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Quiring","sequence":"additional","affiliation":[{"name":"UR 3072, \u201cMitochondria, Oxidative Stress and Muscle Plasticity\u201d, Biomedicine Research Center of Strasbourg (CRBS), Faculty of Medicine, University of Strasbourg, 67081 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8890-3236","authenticated-orcid":false,"given":"Cindy","family":"Barnig","sequence":"additional","affiliation":[{"name":"UR 3072, \u201cMitochondria, Oxidative Stress and Muscle Plasticity\u201d, Biomedicine Research Center of Strasbourg (CRBS), Faculty of Medicine, University of Strasbourg, 67081 Strasbourg, France"},{"name":"Department of Physiology and Functional Explorations, University Hospital of Strasbourg, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margherita","family":"Giannini","sequence":"additional","affiliation":[{"name":"UR 3072, \u201cMitochondria, Oxidative Stress and Muscle Plasticity\u201d, Biomedicine Research Center of Strasbourg (CRBS), Faculty of Medicine, University of Strasbourg, 67081 Strasbourg, France"},{"name":"Department of Physiology and Functional Explorations, University Hospital of Strasbourg, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Meyer","sequence":"additional","affiliation":[{"name":"UR 3072, \u201cMitochondria, Oxidative Stress and Muscle Plasticity\u201d, Biomedicine Research Center of Strasbourg (CRBS), Faculty of Medicine, University of Strasbourg, 67081 Strasbourg, France"},{"name":"Department of Physiology and Functional Explorations, University Hospital of Strasbourg, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Lejay","sequence":"additional","affiliation":[{"name":"UR 3072, \u201cMitochondria, Oxidative Stress and Muscle Plasticity\u201d, Biomedicine Research Center of Strasbourg (CRBS), Faculty of Medicine, University of Strasbourg, 67081 Strasbourg, France"},{"name":"Department of Vascular Surgery, University Hospital of Strasbourg, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0850-1331","authenticated-orcid":false,"given":"Claire","family":"Lugnier","sequence":"additional","affiliation":[{"name":"UR 3072, \u201cMitochondria, Oxidative Stress and Muscle Plasticity\u201d, Biomedicine Research Center of Strasbourg (CRBS), Faculty of Medicine, University of Strasbourg, 67081 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5824-6359","authenticated-orcid":false,"given":"Bernard","family":"Geny","sequence":"additional","affiliation":[{"name":"UR 3072, \u201cMitochondria, Oxidative Stress and Muscle Plasticity\u201d, Biomedicine Research Center of Strasbourg (CRBS), Faculty of Medicine, University of Strasbourg, 67081 Strasbourg, France"},{"name":"Department of Physiology and Functional Explorations, University Hospital of Strasbourg, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Schick, M.A., and Schlegel, N. 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