Spatial and temporal evolution of neuronal activation, stress and injury in lithium-pilocarpine seizures in adult rats

In order to follow the spatial and temporal evolution of neuronal damage, cellular activation and stress responses subsequent to lithium-pilocarpine seizures of various durations in the adult rat, we analyzed the expression of Fos protein and local cerebral glucose utilization as markers of cellular activation, HSP72 immunoreactivity and acid fuchsin staining as indicators of cellular stress and injury, and Cresyl violet staining for the assessment of neuronal damage. The expression of Fos appeared very early, 2-30 min after the onset of polyspikes and intensified during the following 4 h. Fos immunoreactivity was especially high in the hippocampus, cerebral cortex, amygdala and anterior olfactory nuclei. Local cerebral glucose utilization measured during the second hour of seizures was largely increased (350-580%) over control levels in cortical areas, amygdala, dentate gyrus, caudate nucleus and mediodorsal thalamus. HSP72 immunoreactivity never appeared earlier than 40-50 min after the onset of polyspikes, and was most prominent in hippocampal CA3 area, cerebral cortex (except the piriform cortex) and anterior olfactory nuclei. Acid fuchsin staining was maximal in the piriform cortex and the polymorphic layer of the dentate gyrus. Staining was moderate in the sensorimotor cortex and the amygdala. Neuronal damage was extensive in the piriform. and entorhinal cortices, the hippocampal CA3 area and the polymorphic layer of the dentate gyrus, basal amygdala, mediodorsal thalamus and anterior olfactory nuclei. In conclusion, the present study shows that brain regions with the highest expression of Fos and the largest metabolic activation were also highly stained with acid fuchsin and most heavily damaged. Conversely, there is no clear relationship between HSP72 expression, cellular activation and neuronal damage. (C) 1998 Elsevier Science B.V. All rights reserved.