•Interstrain differences were found in the levels of ionotropic glutamate receptor subunits of mice.•The pilocarpine-induced seizures resulted in strain-dependent changes in the distribution of the ionotropic glutamate receptor subunits in the hippocampus.•The seizures reduced the GluA1 and GluA2 densities, the alterations of which in the dentate gyrus were adversely correlated in the individual mice.•The PILO treatment caused sclerotic hippocampi in the NMRI mice, while the Balb/c animals resisted to sclerosis.

Treatment with pilocarpine (PILO) induces variable degrees of loss of mossy cells (MCs) and mossy fibre (MF) sprouting in rodents, the relationships of which have not been examined in individual animals. Our aim was to test whether the loss of MCs and MF sprouting are coupled processes in PILO-treated rodents. Animals which exhibited intense PILO-induced convulsions for at least 30 min were used in this study. After a 2-month survival period, the incidence of epileptic seizures was checked individually by neuropeptide-Y (NPY) immunohistochemistry, and the numbers of MCs were counted by means of immunohistochemistry, for calretinin (CR) in mice and calcitonin gene-related peptide (CGRP) in rats. MF sprouting was checked by using Timm's silver-sulphide method for zinc. In our comparative studies, NPY immunohistochemistry resulted in more positive animals than on zinc staining. The CR immunoreactivity remained unchanged even in those mice that displayed MF sprouting and greatly increased NPY immunoreactivity. CR immunoreactivity was also verified after transection of the fornix to exclude the extrahippocampal source of this peptide. However, the CGRP immunoreactivity was severely reduced in those rats that exhibited simultaneous increases in zinc content and NPY immunoreactivity in the supragranular layer and stratum lucidum. Our findings suggest that the MCs survive PILO treatment in mice, but not in rats. There is direct evidence of a close relationship between the loss of MCs and MF sprouting in rats, but not in mice. Thus, similar PILO seizures may result from different changes in the neuronal circuits of rodents.

Pilocarpine-induced epileptic state (Status epilepticus) generates an aberrant sprouting of hippocampal mossy fibers, which alter the intrahippocampal circuits. The mechanisms of the synaptic plasticity remain to be determined. In our studies in mice and rats, pilocarpine-induced seizures were done in order to gain information on the process of synaptogenesis. After a 2-month survival period, changes in the levels of synaptic markers (GAP-43 and Syn-I) were examined in the hippocampus by means of semi-quantitative immunohistochemistry. Mossy fiber sprouting (MFS) was examined in each brain using Timm's sulphide-silver method. Despite the marked behavioral manifestations caused by pilocarpine treatment, only 40% of the rats and 56% of the mice showed MFS. Pilocarpine treatment significantly reduced the GAP-43 immunoreactivity in the inner molecular layer in both species, with some minor differences in the staining pattern. Syn-I immunohistochemistry revealed species differences in the sprouting process. The strong immunoreactive band of the inner molecular layer in rats corresponded to the Timm-positive ectopic mossy fibers. The staining intensity in this layer, representing the ectopic mossy fibers, was weak in the mouse. The Syn-I immunoreactivity decreased significantly in the hilum, where Timm's method also demonstrated enhanced sprouting. This proved that, while sprouted axons displayed strong Syn-I staining in rats, ectopic mossy fibers in mice did not express this synaptic marker. The species variability in the expression of synaptic markers in sprouted axons following pilocarpine treatment indicated different synaptic mechanisms of epileptogenesis.

Kynurenic acid (KYNA) is the only known endogenous N-methyl-d-aspartate (NMDA) receptor inhibitor and might therefore come into consideration as a therapeutic agent in certain neurobiological disorders. However, its use as a neuroprotective compound is practically excluded because KYNA does not readily cross the blood-brain barrier (BBB). We recently synthetized a new compound, glucosamine–kynurenic acid (KYNA-NH-GLUC), which is presumed to cross the BBB more easily. In this study, the effects of KYNA and KYNA-NH-GLUC on behavior and cortical activity were investigated in adult rats. The results show that (1) on intracerebroventricular application, the behavioral changes induced by KYNA and by KYNA-NH-GLUC are quite similar; (2) on intravenous administration, KYNA (25 mg/kg) has no effect on the somatosensory-evoked cortical potentials, whereas KYNA-NH-GLUC (25 mg/kg) causes transient but appreciable reductions in the amplitudes of the evoked responses within 5 min after application; and (3) the results of in vitro studies demonstrated that both KYNA and KYNA-NH-GLUC reduced the amplitudes of the field excitatory postsynaptic potentials (fEPSPs). These observations suggest that the two compounds have similar effects, but that KYNA-NH-GLUC passes the BBB much more readily than does KYNA. These results imply that the conjugated NH-GLUC is of importance in the passage across the BBB.