title: Minocycline treatment prevents cavitation in rats after a cortical devascularizing lesion.
abstract: Minocycline, a second-generation tetracycline, has been shown to possess neuroprotective effects in animal models of stroke. Pial vessel disruption in adult Wistar rats leads to a cone-shaped cortical lesion and turns into a fluid-filled cavity surrounded by a GFAP+ glia limitans 21 days after injury. This mimics the clinical situation in lacunar infarcts. Minocycline was given intraperitoneally at a dose of 45 mg/kg 1 and 12 h after lesioning, followed by 22.5 mg/kg twice daily until 6 days after lesioning. Control rats received intraperitoneal injections of equivalent volumes of saline. Cavitation was prevented in five out of six minocycline-treated animals and the glia limitans did not appear as the space was filled with GFAP+ reactive astrocytes. However, the number of activated microglia showed no difference between minocycline-treated and -untreated groups. Minocycline did not reduce the number of infiltrating leukocytes, predominately polymorphonuclear neutrophils (PMNs) determined by myeloperoxidase immunoreactivity, or infiltration of CD3+ lymphocytes. The pial vessel occlusion induced a significant upregulation of IL-1beta expression; however, minocycline treatment did not significantly alter this upregulation of IL-1beta. In this study, we found minocycline facilitated the repopulation of the lesion by reactive astrocytes and therefore prevented cavitation; however, we could not identify the molecular signal.
authors.affiliation: Department of Physiology, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Canada SK S7N 5E5.
authors.forename: Rui
authors.initials: R
authors.lastname: Hua
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Walz
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy / Q000503:physiopathology; D002536:Cerebral Arteries / Q000293:injuries / Q000503:physiopathology / Q000601:surgery; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D007375:Interleukin-1 / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology* / Q000627:therapeutic use; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; D018696:Neuroprotective Agents; D008911:Minocycline