Comparison of ibotenate and kainate neurotoxicity in rat brain: a histological study

The neurotoxic properties of ibotenate and kainate after intracerebral application were compared in several regions of the rat brain. Ibotenate, being 5-10 times less toxic than kainate, caused lesions which were generally found to extend spherically from the tip of the injection cannula. In contrast, kainate injections often resulted in neuronal degeneration distant from the site of infusion, thus severely limiting its use as a tool for causing lesions in neurobiological studies. In some of the brain regions examined (hippocampus, septum), neurons appeared differentially susceptible to kainate but uniformly vulnerable to ibotenate. Some cell groups, such as those in the medial septum and the locus coeruleus, proved highly resistant to kainate but could be selectively ablated by ibotenate. These findings, together with differences between the two toxins in the evolution of neuronal degeneration (exemplified here in the hippocampal formation), appear to support previous suggestions that ibotenate and kainate exert their excitotoxic actions via different mechanisms. On the other hand, neuropathological changes caused in the cerebellum did not differ, since both ibotenate and kainate preferentially destroyed granule cells. Two nuclei, the arcuate nucleus of the hypothalamus and the nucleus of the fifth nerve, were found to be extremely resistant to either neurotoxin.