Neuroprotective effects of IGF-I following kainic acid-induced hippocampal degeneration in the rat.
Insulin-like growth factor I (IGF-I) has been shown to act as a neuroprotectant both in in vitro studies and in in vivo animal models of ischemia, hypoxia, trauma in the brain or the spinal cord, multiple and amyotrophic lateral sclerosis, Alzheimer's and Parkinson's disease. In the present study, we investigated the neuroprotective potential of IGF-I in the "kainic acid-induced degeneration of the hippocampus" model of temporal lobe epilepsy. Increased cell death--as detected by FluoroJade B staining--and extensive cell loss--as determined by cresyl violet staining--were observed mainly in the CA3 and CA4 areas of the ipsilateral and contralateral hippocampus, 7 days following intrahippocampal administration of kainic acid. Kainic acid injection also resulted in intense astrogliosis--as assessed by the number of glial fibrillary acidic protein (GFAP) immunopositive cells--in both hemispheres, forming a clear astroglial scar ipsilaterally to the injection site. Heat-shock protein 70 (Hsp70) immunopositive cells were also observed in the ipsilateral dentate gyrus (DG) following kainic acid injection. When IGF-I was administered together with kainic acid, practically no signs of degeneration were detected in the contralateral hemisphere, while in the ipsilateral, there was a smaller degree of cell loss, reduced number of FluoroJade B-stained cells, decreased reactive gliosis and fewer Hsp70-positive cells. Our present results extend further the cases in which IGF-I is shown to exhibit neuroprotective properties in neurodegenerative processes in the CNS.
Biology-Biochemistry Laboratory, Department of Basic Sciences, Faculty of Nursing, School of Health Sciences, University of Athens, Papadiamantopoulou 123, 11527, Greece.
Panagiota
P
Miltiadous
Antonios
A
Stamatakis
Fotini
F
Stylianopoulou
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000150:complications*; D005452:Fluoresceins; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D050884:HSP72 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000627:therapeutic use; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D009930:Organic Chemicals; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology
D015415:Biomarkers; D005452:Fluoresceins; D005904:Glial Fibrillary Acidic Protein; D050884:HSP72 Heat-Shock Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009930:Organic Chemicals; C435731:fluoro jade; D007334:Insulin-Like Growth Factor I; D007608:Kainic Acid