Pentoxifylline and insulin-like growth factor-I (IGF-I) abrogate kainic acid-induced cognitive impairment in mice

• Published in: Journal of neuroimmunology 2005-12, Vol.169 (1), p.50-58
• Main Authors: Bluthé, Rose-Marie, Frenois, François, Kelley, Keith W., Dantzer, Robert
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Behavior, Animal; Cognition Disorders - chemically induced; Cognition Disorders - drug therapy; Cognition Disorders - pathology; Discrimination Learning - drug effects; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Fluoresceins; Free Radical Scavengers - therapeutic use; Hippocampus - cytology; Hippocampus - drug effects; Insulin-Like Growth Factor Binding Protein 1 - therapeutic use; Insulin-like growth factor-I; Kainic Acid; Male; Mice; Mice, Inbred ICR; Motor Activity - drug effects; Mouse; Nerve Degeneration - chemically induced; Nerve Degeneration - drug therapy; Nerve Degeneration - pathology; Neurons - drug effects; Organic Chemicals - metabolism; Pentoxifylline; Pentoxifylline - therapeutic use; Spatial memory; Tumor necrosis factor-alpha
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2005.07.017

Hippocampal insults involving neuroimmune mechanisms can impair learning and memory in a variety of tasks. The present study was designed to assess the effect of pentoxifylline, an inhibitor of tumor necrosis factor alpha (TNFα), and insulin-like growth factor-I (IGF-I) on kainate (KA)-induced impairment in spatial memory. Male mice received a subcutaneous injection of a dose of KA (15 mg/kg) that had no cytotoxic effect on hippocampal neurons as confirmed by Fluorojade B staining. This dose resulted in an impairment of spatial memory in a two-trial recognition task 11 days later. Intraperitoneal administration of pentoxifylline (200 mg/kg) abrogated this effect. Repeated intracerebroventricular injection of IGF-I (2 μg/mouse on day 1 followed by 1 μg/mouse on days 2–5) abrogated KA-induced deficits in spatial memory whereas acute IGF-I (2 μg/mouse on day 1 only) had mixed effects. These findings indicate that endogenous TNFα is probably involved in the detrimental effects of kainate on cognition and that exogenous IGF-I can oppose these effects, probably by antagonizing TNFα-induced neurotoxicity.