Np031112, a Thiadiazolidinone Compound, Prevents Inflammation and Neurodegeneration Under Excitotoxic Conditions: Potential Therapeutic Role in Brain Disorders.
From: Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28029 Madrid, Spain.
The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publish Date: May 2007
- ISSN: 1529-2401
- Volume: 27
- Issue: 21
- Pages: 5766-76
- Medium: Internet
- Language: English
- Citation (JAMA): Luna-Medina Rosario, Cortes-Canteli Marta, Sanchez-Galiano Susana, et al. Np031112, a Thiadiazolidinone Compound, Prevents Inflammation and Neurodegeneration Under Excitotoxic Conditions: Potential Therapeutic Role in Brain Disorders.. J. Neurosci. May 2007;27:5766-76
Abstract
Inflammation 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.
Mesh Headings (Keywords): Animals, Anti-Inflammatory Agents, Non-Steroidal, Brain Diseases, Brain Edema, Cell Death, Cells, Cultured, Excitatory Amino Acid Agents, Glutamic Acid, Inflammation, Male, Nerve Degeneration, Neuroprotective Agents, Rats, Rats, Wistar, Thiadiazoles
Check for Full Text / PubMed Unique Identifier (PMID): 17522320
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