期刊
EXPERIMENTAL NEUROLOGY
卷 231, 期 2, 页码 223-235出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2011.06.014
关键词
IGF-I; Kainic acid; Hippocampal degeneration; FluoroJade B; GFAP; Microglia; Adult hippocampal neurogenesis; Morris water maze; Learning and memory; Temporal lobe epilepsy
资金
- Greek Ministry of Development-General Secretariat of Research and Technology
- E.U.
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. (C) 2011 Elsevier Inc. All rights reserved.
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