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Neuroprotection from Tissue Inhibitor of Metalloproteinase-1 and its nanoparticles.
MedLine Citation:
PMID:  22892277     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Matrix metalloproteinases (MMPs) are family of zinc dependent endopeptidases, which cleave extracellular matrix proteins, and play an important role in tissue remodelling in physiological and pathological processes. There is enhanced expression of MMPs, in particular MMP-9, during numerous pathological conditions, including epilepsy and ischemic stroke. Therefore, inhibition of MMP-9 is considered as a potential therapeutic target. Tissue Inhibitor of Matrix Metalloproteinase-1 (TIMP-1) is a 28kDa endogenous inhibitor of MMP-9. In this study we examined recombinant mouse TIMP-1 for its in-vitro neuroprotective effects, against Kainic Acid (KA) induced excitotoxicity in organotypic hippocampal slice culture (OHC) model. We also studied, sustained release effects of TIMP-1 in OHC by using poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs). TIMP-1 and TIMP-1 PLGA NPs were added to the slice cultures at different time points, i.e., 30min before treatment with KA and 6h after KA treatment. Propidium iodide staining was used to reveal cell toxicity in the cultures. In addition, neurotoxicity was assessed using standard lactate dehydrogenase (LDH) release assay. Gelatinolytic activity in conditioned cultured medium of OHC was accessed by a fluorescent substrate assay. Briefly, our result show that TIMP-1 provided significant level of neuroprotection, especially when given before 30min of KA and released from the NPs. Since gelatinolytic activity assay showed a decrease in MMP-9 activity, it can be suggested that this neuroprotection might be mediated by the gelatinase inhibition.
Authors:
Mayank Chaturvedi; Izabela Figiel; Bojja Sreedhar; Leszek Kaczmarek
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-7
Journal Detail:
Title:  Neurochemistry international     Volume:  -     ISSN:  1872-9754     ISO Abbreviation:  Neurochem. Int.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ltd.
Affiliation:
Laboratory of Neurobiology, Department of Molecular & Cellular Neurobiology, Nencki Institute, Pasteura 3, 02-093 Warsaw, Poland; Inorganic & Physical Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500 607, India.
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