Neuroprotective Effects of IGF-I Following Kainic Acid-Induced Hippocampal Degeneration in the Rat

Abstract

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.

Plasma Insulin-Like Growth Factor 1 Is Associated with Cognitive Impairment in Parkinson's Disease

“…This hypothesis was supported by animal model studies which showed that IGF-1 supplement prevented the loss of dopaminergic neurons [11]. In an AD model, IGF-1 also showed a protective effect on hippocampus degeneration [12], further supporting the protective role of IGF-1 in neurodegenerative diseases. However, we did not find any change of plasma IGF-1 in ET patients in our study.…”

Rediscovering area CA2: unique properties and functions

“…These possible mechanisms include the superior calcium-handling capacity of CA2 pyramidal neurons compared with that of neurons in other CA areas 68 and the high expression levels of molecules associated with neuroprotection, such A1Rs 77,111 and receptors and binding partners for growth factors, which have been shown to promote neuronal survival and reduce seizure activity in animal models 112,113 . Indeed, local administration of insulin-like growth factor 1 (IGF1) has been shown to reduce seizure severity and decrease neuronal loss in animal and cell culture models of epilepsy 114,115 , which may be attributable to the high expression levels of the IGF1 receptor and IGF-binding protein 4 in rodent CA2 neurons 116,117 . In addition, somatostatin receptor 5, which negatively couples to voltage-gated calcium channels, is highly expressed in CA2 neurons, as shown in gerbils 118 , and may contribute to protection of CA2 neurons from insults that trigger calcium influx.…”

Pathophysiogenesis of Mesial Temporal Lobe Epilepsy: Is Prevention of Damage Antiepileptogenic?

“…Overall, GH, GHSs, like ghrelin and cognate molecules, and IGF-1 have been found to exert neuroprotective effects in different models [306, 307], including kainate-induced SE [308, 309], the pilocarpine model [310], cerebral ischemia [311, 312], and models of neurodegenerative diseases [313]. Notably, rats in which IGF-1 was administered intracerebrally together with kainate, no signs of degeneration were detected in the contralateral hemisphere, whereas ipsilateral cell loss, assessed by Fluoro-Jade B staining, was consistently reduced, in association with less reactive gliosis [314].…”