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Title

NP031112, a thiadiazolidinone compound, prevents inflammation and neurodegeneration under excitotoxic conditions: potential therapeutic role in brain disorders

AuthorsLuna Medina, Rosario de CSIC; Cortés-Canteli, Marta CSIC ORCID; Sánchez-Galiano, Susana; Morales-García, José A. CSIC ORCID; Martínez, Ana CSIC ORCID ; Santos, Ángel; Pérez Castillo, Ana CSIC ORCID
KeywordsExcitotoxicity
Neurodegenerative diseases
Neuroinflammation
Neuroprotection
Peroxisome proliferator-activated receptor
Thiadiazolidinones
Issue Date23-May-2007
PublisherSociety for Neuroscience
CitationJournal of Neuroscience 27(21): 5766-5776 (2007)
AbstractInflammation and neurodegeneration coexist in many acute damage and chronic CNS disorders (e.g., stroke, Alzheimer's disease, Parkinson's disease). A well characterized animal model of brain damage involves administration of kainic acid, which causes limbic seizure activity and subsequent neuronal death, especially in the CA1 and CA3 pyramidal cells and interneurons in the hilus of the hippocampus. Our previous work demonstrated a potent anti-inflammatory and neuroprotective effect of two thiadiazolidinones compounds, NP00111 (2,4-dibenzyl-[1,2,4]thiadiazolidine-3,5-dione) and NP01138 (2-ethyl-4-phenyl-[1,2,4]thiadiazolidine-3,5-dione), in primary cultures of cortical neurons, astrocytes, and microglia. Here, we show that injection of NP031112, a more potent thiadiazolidinone derivative, into the rat hippocampus dramatically reduces kainic acid-induced inflammation, as measured by edema formation using T2-weighted magnetic resonance imaging and glial activation and has a neuroprotective effect in the damaged areas of the hippocampus. Last, NP031112-induced neuroprotection, both in vitro and in vivo, was substantially attenuated by cotreatment with GW9662 (2-chloro-5-nitrobenzanilide), a known antagonist of the nuclear receptor peroxisome proliferator-activated receptor gamma, suggesting that the effects of NP031112 can be mediated through activation of this receptor. As such, these findings identify NP031112 as a potential therapeutic agent for the treatment of neurodegenerative disorders.
Description11 pages, 6 figures.
Publisher version (URL)http://dx.doi.org/10.1523/JNEUROSCI.1004-07.2007
URIhttp://hdl.handle.net/10261/24810
DOI10.1523/JNEUROSCI.1004-07.2007
ISSN0270-6474
Appears in Collections:(IIBM) Artículos




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