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

Spatial memory is enhanced in long-living Ames dwarf mice and maintained following kainic acid induced neurodegeneration

“…In the hippocampus, the highest density of KA receptors is found in the CA3 subfield, the area most severely damaged following KA administration. The neuronal injury with kainic acid in our study corresponded with that reported in other studies that used FluoroJade as a marker of neuronal loss (Bluthe et al, 2005; Mazarati et al, 2004). We used FJC as a marker of neuronal degeneration as it is sensitive and it specifically binds to degenerating neurons but not to healthy neurons, myelin, or vascular elements (Schmued et al, 1997, 2005; Schmued and Hopkins, 2000a,b).…”

“…Wild type mice with 15 mg/kg KA did not show deficiencies in memory like those with the higher dose possibly because lower “subconvulsive” doses of KA are not great enough for deterioration of spatial memory (rats; Arkhipov et al, 2008). A conflicting report in mice however, showed that systemic injection of KA at a dose that does not induce seizures or neuronal degeneration is able to impair spatial memory (Bluthe et al, 2005). One other possible reason for an increase in the number of errors after KA-induced neuronal loss could be due to a defect in selective attention.…”

“…We believe that even though hippocampal IGF-1 levels were not higher in Ames dwarf mice, the locally produced IGF-1 might have different effects as compared to peripheral IGF-1 in wild type mice. IGF-1 has been shown to abrogate KA-induced memory impairment but the role of IGF-1 and effect of KA on neurogenesis needs further exploration by studying the time course of neurogenesis after KA injection in both wild type and Ames dwarf mice and the correlation with spatial memory (Bluthe et al, 2005). Increases in IGF-1 mRNA levels have been reported in non-brain tissue with age in Ames dwarf mice as opposed to decreases in wild type mice (Swindell, 2007).…”

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

“…These results show that IGF-I can act as a neuroprotectant following kainic acid-induced hippocampal degeneration. Our present findings, together with those of Bluthé et al (2005) who showed that IGF-I can ameliorate kainic acid-induced cognitive deficiency as measured in the Y maze, document that IGF-I has neuroprotective properties in another animal model of neurodegeneration: kainic acid-induced hippocampal degeneration, in addition to those previously reported (ischemia, hypoxia, brain injury etc. ).…”

Kainate-induced epileptogenesis alters circular hole board learning strategy but not the performance of C57BL/6J mice

“…However, other behavioral tasks to test hippocampal functioning in mice are available, and several of them have indeed been used to monitor seizureinduced cognitive impairments in different mouse strains (Table 1). Both the strain and behavioral model used are of importance, and in general, studies show decreased spontaneous alterations in the Ymaze [15,26], a decreased latency in the passive avoidance task [11][12][13]15,27], and an impaired retention transfer latency [27], all pointing towards cognitive impairments. Thus, the processes that take place in the brain during and after seizures can have a significant effect on cognitive and emotional behavior including spatial memory and anxiety [3,28].…”