title: Lack of resveratrol neuroprotection in developing rats treated with kainic acid.
abstract: In adult rats, trans-resveratrol attenuates kainic acid (KA)-induced convulsions and the associated hippocampal neurotoxicity. Increased neuronal survival was correlated with reduced lipid peroxidation. Since free radical generation after KA is age dependent and does not correlate with the onset of seizure-induced injury, the present study investigated whether daily trans-resveratrol treatment in development could protect the juvenile hippocampus from seizures and onset of damage at postnatal (P) day 21. Rat pups were treated with daily injections of trans-resveratrol under three dosage regimens (1-15 mg/kg and 20-50mg/kg). Weight, electroencephalography (EEG), histology, and N-methyl-d-aspartate (NMDA) receptor expression were determined. Malondialdehyde (MDA) concentration was assessed from separate animals. trans-Resveratrol did not interfere with growth or attenuate KA-induced EEG seizures. However, modest protection was afforded in the CA1, the subregion most sensitive to injury at this age. The CA3 and entorhinal amygdala cortex (AMG/EC) were not spared. Changes in NR1 subunit or NR1 C2 splice variant expression were also not prevented. Baseline MDA concentrations of hippocampal subfields were low at P14, P21, and P60 and high in aged adults. Glutamate (100 μM) to stimulate peroxidation products was significant at young ages but was much greater at older ages. After KA, elevated MDA levels were observed at 24h but only in adult preparations. Thus, while antioxidant therapy with trans-resveratrol may be considered as an adjunctive therapy to hinder epileptic activity and neurodegeneration at adult ages, it had only modest effects at young ages when production of free radicals within limbic structures is limited in this experimental model of seizures.
authors.affiliation: New York Medical College, Valhalla, NY 10595, United States. Linda_Friedman@nymc.edu
authors.forename: L K
authors.initials: LK
authors.lastname: Friedman
authors.forename: B
authors.initials: B
authors.lastname: Goldstein
authors.forename: A
authors.initials: A
authors.lastname: Rafiuddin
authors.forename: P
authors.initials: P
authors.lastname: Roblejo
authors.forename: S
authors.initials: S
authors.lastname: Friedman
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D058256:Brain Waves / Q000187:drug effects; D002452:Cell Count; D004195:Disease Models, Animal; D004569:Electroencephalography; D018690:Excitatory Amino Acid Agonists / Q000627:therapeutic use*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development; D007608:Kainic Acid / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D000077185:Resveratrol; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy*; D013267:Stilbenes / Q000627:therapeutic use*
chemical_list: D018690:Excitatory Amino Acid Agonists; C409466:NR1 NMDA receptor; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D013267:Stilbenes; D008315:Malondialdehyde; D010751:Phosphopyruvate Hydratase; D000077185:Resveratrol; D007608:Kainic Acid