title: IGF-I ameliorates hippocampal neurodegeneration and protects against cognitive deficits in an animal model of temporal lobe epilepsy.
abstract: Epilepsy is a major neurological disease, and patients often show spatial memory deficits. Thus, there is a need of effective new therapeutic approaches. IGF-I has been shown to be neuroprotective following a number of experimental insults to the nervous system, and in a variety of animal models of neurodegenerative diseases. In the present work, we investigated the possible neuroprotective effects of IGF-I following unilateral intrahippocampal administration of kainic acid (KA), an animal model of temporal lobe epilepsy (TLE). KA induced cell death, as shown by FluoroJade B, and extensive cell loss in both the ipsilateral and contralateral CA3 and CA4 areas, as well as granule cell dispersal in the DG, as revealed by Cresyl violet staining. KA also resulted in intense astrogliosis and microgliosis, as assessed by the number of GFAP and CD11b immunopositive cells, respectively, and increased hippocampal neurogenesis. Exposure to the Morris Water Maze task revealed that mice injected with KA were deficient in spatial learning and both short- and long-term memories, when tested in a larger diameter pool, which requires the use of allocentric strategies. When tested in a smaller pool, only long-term memory was impaired. Administration of IGF-I decreased seizure severity, hippocampal neurogenesis, and protected against neurodegeneration at the cellular level as assessed by FluoroJade B and Cresyl violet staining, as well as the number of GFAP and CD11b immunopositive cells. Furthermore, IGF-I abolished the cognitive deficits. Our results support that IGF-I could have a possible therapeutic potential in TLE.
authors.affiliation: Biology-Biochemistry Lab, Dept. Basic Sciences, Faculty of Nursing, School of Health Sciences, University of Athens, Papadiamantopoulou 123, GR-11527, Greece.
authors.forename: Panagiota
authors.initials: P
authors.lastname: Miltiadous
authors.forename: Antonios
authors.initials: A
authors.lastname: Stamatakis
authors.forename: Paraskevi N
authors.initials: PN
authors.lastname: Koutsoudaki
authors.forename: Dina G
authors.initials: DG
authors.lastname: Tiniakos
authors.forename: Fotini
authors.initials: F
authors.lastname: Stylianopoulou
mesh_terms: D000818:Animals; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology
chemical_list: D018690:Excitatory Amino Acid Agonists; D007334:Insulin-Like Growth Factor I; D007608:Kainic Acid