title: Early reperfusion injury is associated to MMP2 and IL-1β elevation in cortical neurons of rats subjected to middle cerebral artery occlusion.
abstract: The pathophysiological processes implicated in ischemic brain damage are strongly affected by an inflammatory reaction characterized by activation of immune cells and release of soluble mediators, including cytokines and chemokines. The pro-inflammatory cytokine interleukin (IL)-1β has been implicated in ischemic brain injury, however, to date, the mechanisms involved in the maturation of this cytokine in the ischemic brain have not been completely elucidated. We have previously suggested that matrix metalloproteinases (MMPs) may be implicated in cytokine production under pathological conditions. Here, we demonstrate that significant elevation of IL-1β occurs in the cortex as early as 1h after the beginning of reperfusion in rats subjected to 2-h middle cerebral artery occlusion (MCAo). At this early stage, we observe increased expression of IL-1β in pericallosal astroglial cells and in cortical neurons and this latter signal colocalizes with elevated gelatinolytic activity. By gel zymography, we demonstrate that the increased gelatinolytic signal at 1-h reperfusion is mainly ascribed to MMP2. Thus, MMP2 seems to contribute to early brain elevation of IL-β after transient ischemia and this mechanism may promote damage since pharmacological inhibition of gelatinases by the selective MMP2/MMP9 inhibitor V provides neuroprotection in rats subjected to transient MCAo.
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Italy. Electronic address: amantea@unical.it.
authors.forename: D
authors.initials: D
authors.lastname: Amantea
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Certo
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Russo
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bagetta
authors.affiliation: Department of Health Sciences, University Magna Graecia of Catanzaro, Italy.
authors.forename: M T
authors.initials: MT
authors.lastname: Corasaniti
authors.affiliation: IRCCS National Neurological Institute C. Mondino Foundation, Pavia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Tassorelli
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005780:Gelatin / Q000378:metabolism; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D011897:Random Allocation; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology*; D013997:Time Factors
chemical_list: C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D061965:Matrix Metalloproteinase Inhibitors; D018696:Neuroprotective Agents; C014567:Gelatinol; D005780:Gelatin; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: IL-1β; brain ischemia; matrix metalloproteinases; neuroinflammation