Abstracts

Rationale: Astrogliosis and microglial activation occur following brain insults including stroke, traumatic brain injury and seizures. It is becoming increasingly clear that glial cells play a critical role in the ensuing effects on neuronal degeneration and survival. Thus, it is important to understand the precise temporal and spatial changes for glial cells following injury to the brain, so that therapeutic intervention can be directed at the appropriate timepoints and targets. The rodent pilocarpine model of temporal lobe epilepsy is well-suited for neuroanatomical studies because several changes occur in the hippocampus that closely mimic the human condition. These include: cell death, mossy fiber sprouting, basal dendrite formation on granule cells, aberrant synaptogenesis, astrogliosis and microglial activation. The current study examined rapid astrocyte and microglial changes in the hippocampus during the first five days (and also at 8 days) after pilocarpine-induced seizures. Methods: Sections of hippocampus were immunocytochemically processed with antibodies to S100B and GFAP for astrocyte labeling, and IBA-1 for microglial cells. Images from selected regions were analyzed using ImageTool software to calculate the number of pixels for the labeled structures in each type of preparation. Results: The results show that S100B labeling is elevated in CA1, CA3 and the hilus by 1 day following pilocarpine-induced seizures. The S100B labeling continues to increase in the following two days. However, at 4 days after seizures are induced, the level of S100B immunolabeling begins to decline and nears baseline levels at 5 days following seizures. GFAP immunolabeling is increased in the hilus, but not in CA1 or CA3 at 1 day after pilocarpine-induced siezures. This initial increase in the hilus is followed by a transient decrease on day 2 and a persistent decrease in CA1 on day 3. At day 4, all regions show increased labeling for GFAP+ astrocytes. The temporal pattern of labeling for microglial cells was different in that there was an immediate increase in IBA-1 labeling in all three of these hippocampal regions at 1day, which declined from day 2 through 5, then increased again at day 8. It is pertinent to note that on all of the days examined, the IBA-1-labeling was greater for all three regions, when compared to the controls. Conclusions: The transient decrease of GFAP labeling in the hilus after seizures could be explained by astrocyte death. The increase that follows is consistent with previous data that suggests astrocyte profiferation occurs following S100B and microglial increases. The pattern of IBA-1 immunoreactivity is consistent with microglial activation immediately after seizures. The data will be discussed in the context of previously described neuroplastic changes following seizures.