title: Protective roles of nanomelatonin in cerebral ischemia-reperfusion of aged brain: Matrixmetalloproteinases as regulators.
abstract: Cerebral ischemia-reperfusion (CIR) injury occurs as a result of oxygen occlusion in the carotid artery through embolus or thrombus formation or cerebrovascular hemorrhage. The oxygen thrust during reperfusion causes the generation of reactive oxidative species (ROS) which exert a potential threat to neuronal survival. ROS may possibly be arrested by antioxidants. After CIR, extracellular matrix remodeling takes place, which is governed by matrix metalloproteinases (MMPs). Augmentation of lipid per oxidation, perturbation of antioxidant enzyme activities and the loss of pyramidal neuronal cells in rat brain were attributed to CIR injury. Melatonin can readily cross the blood-brain barrier (BBB) to exert protective effects as an antioxidant but it is quickly cleared by the circulating blood. Also melatonin is easily degraded by light and hence is found to be ineffective during daytime. Results of the present study showed that unlike free melatonin (FM), the application of nanocapsulated melatonin (NM) exhibited significantly higher potential even at much lower concentrations to rescue neuronal cells and mitochondria during CIR insult and also restored the activities of antioxidative enzymes and MMPs to their normal levels. Hence, nanoencapsulated melatonin may be considered as a suitable drug delivery system for brain to exert protection against CIR injury.
authors.affiliation: Drug Development Diagnotics and Biotechnology Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India.
authors.forename: Sibani
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Drug Development Diagnotics and Biotechnology Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Drug Development Diagnotics and Biotechnology Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India.
authors.forename: Nirmalendu
authors.initials: N
authors.lastname: Das
authors.affiliation: Drug Development Diagnotics and Biotechnology Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India. Electronic address: sikta@iicb.res.in.
authors.forename: Snehasikta
authors.initials: S
authors.lastname: Swarnakar
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008550:Melatonin / Q000737:chemistry / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D053769:Nanocapsules / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy*
chemical_list: D000975:Antioxidants; D053769:Nanocapsules; D017382:Reactive Oxygen Species; D020782:Matrix Metalloproteinases; D008550:Melatonin
keywords: Blood-brain barrier; Cerebral ischemia-reperfusion; Matrix metalloproteinase; Nanoencapsulated melatonin; Reactive oxygen species