Glutamine synthetase (GS) is an astrocytic enzyme, which catalyzes the synthesis of glutamine from glutamate and ammonia. In the central nervous system, GS prevents glutamate-dependent excitotoxicity and detoxifies nitrogen. Reduction in both expression and activity of GS was reported in the hippocampus of patients with temporal lobe epilepsy (TLE), and this reduction has been suggested to contribute to epileptogenesis. In this study, we characterized hippocampal GS expression in the pilocarpine model of TLE in Wistar rats by means of stereology and morphometric analysis. Neither the GS positive cell number nor the GS containing cell volume was found to be altered in different hippocampal subregions of chronic epileptic rats when compared with controls. Instead, redistribution of the enzyme at both intracellular and tissue levels was observed in the epileptic hippocampus; GS was expressed more in proximal astrocytic branches, and GS expressing astrocytic somata was located in closer proximity to vascular walls. These effects were not due to shrinkage of astrocytic processes, as revealed by glial fibrillary acidic protein staining. Our results argue for GS redistribution rather than downregulation in the rat pilocarpine model of TLE. The potential contribution of increased GS perivascular affinity to the pathogenesis of epilepsy is discussed as well.

Activation of microglial cells (brain macrophages) soon after status epilepticus has been suggested to be critical for the pathogenesis of mesial temporal lobe epilepsy (MTLE). However, microglial activation in the chronic phase of experimental MTLE has been scarcely addressed. In this study, we questioned whether microglial activation persists in the hippocampus of pilocarpine-treated, epileptic Wistar rats and to which extent it is associated with segmental neurodegeneration. Microglial cells were immunostained for the universal microglial marker, ionized calcium-binding adapter molecule-1 and the activation marker, CD11b (also known as OX42, Mac-1). Using quantitative morphology, i.e., stereology and Neurolucida-based reconstructions, we investigated morphological correlates of microglial activation such as cell number, ramification, somatic size and shape. We find that microglial cells in epileptic rats feature widespread, activation-related morphological changes such as increase in cell number density, massive up-regulation of CD11b and de-ramification. The parameters show heterogeneity in different hippocampal subregions. For instance, de-ramification is most prominent in the outer molecular layer of the dentate gyrus, whereas CD11b expression dominates in hilus. Interestingly, microglial activation only partially correlates with segmental neurodegeneration. Major neuronal death in the hilus, CA3 and CA1 coincides with strong up-regulation of CD11b. However, microglial activation is also observed in subregions that do not feature neurodegeneration, such as the molecular and granular layer of the dentate gyrus. This in vivo study provides solid experimental evidence that microglial cells feature widespread heterogeneous activation that only partially correlates with hippocampal segmental neuronal loss in experimental MTLE.