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Status epilepticus (SE) induced by pilocarpine or kainate is associated with yet not systemically investigated astrocytic and vascular injuries. To investigate their possible association with neuronal damage, the changes in glial fibrillary acidic protein (GFAP), laminin and neuron-specific nuclear protein (NeuN) immunoreactivities were analyzed in rats treated with pilocarpine (380 mg/kg) or kainate (15 mg/kg), and receiving diazepam (20 mg/kg) after 10 min of SE. A different group of rats was injected with endothelin-1 (ET-1) in the caudate putamen to reproduce the changes in GFAP and laminin immunoreactivities associated with ischemia. Focal loss of GFAP immunostaining was accompanied by increased laminin immunoreactivity in blood vessels, in all the examined groups. Regression analysis revealed a significant ( P < 0.01) relationship between astrocytic lesion and increased laminin immunoreactivity in the piriform cortex (Pir) of both pilocarpine ( R 2 = 0.88) and kainate ( R 2 = 0.94) groups of treatment. A significant relationship ( P < 0.01; R 2 = 0.81) was also present in the cornu Ammonis 3 (CA3) hippocampal region of pilocarpine-treated rats. At variance, neuronal and glial lesions were significantly related ( P < 0.05, R 2 = 0.74) only in the substantia nigra of pilocarpine-treated rats. The ratio between areas of GFAP and laminin changes of immunoreactivity in the ET-1 group was similar to those found in pilocarpine- and kainate-treated rats in specific brain regions, such as the hippocampal CA3 subfield, Pir and the anterior olfactory nucleus. The amygdala and submedius thalamic nucleus in the pilocarpine group, and the perirhinal and entorhinal cortices in the kainate group, also presented ischemic-like changes. These results indicate that laminin immunoreactivity is upregulated in the basal lamina of blood vessels after SE induced by pilocarpine or kainate. This phenomenon is significantly associated with lesions involving more glial than neuronal cells, in specific cerebral regions. [ABSTRACT FROM AUTHOR]

We investigated the interference of protein-kinase C (PKC)-dependent Na+ channel phosphorylation on the inhibitory effect that the antiepileptic drug topiramate (TPM) has on persistent Na+ currents (INaP) by making whole cell patch-clamp and intracellular recordings of rat sensorimotor cortex neurons.The voltage-dependent activation of INaP was significantly shifted in the hyperpolarizing direction when PKC was activated by 1-oleoyl-2-acetyl-sn-glycerol (OAG). TPM reduced the peak amplitude of INaP, but it did not counteract the OAG-induced shift in INaP activation. Firing property experiments showed that the firing threshold was lowered by OAG. TPM was unable to counteract this effect, which may be due to OAG-dependent enhancement of the contribution of subthreshold INaP.These data suggest that PKC activation may limit the effect of the anticonvulsant TPM on the persistent fraction of Na+ currents. The channel phosphorylation that may occur in cortical neurons as a result of physiological or pathological (e.g. epileptic) events can modulate the action of TPM on Na+ currents. [Copyright &y& Elsevier]

Abstract: Field and intracellular recordings were made in an in vitro slice preparation to establish whether the antiepileptic drugs topiramate and lamotrigine modulate cholinergic excitation in the rat subiculum. Bath application of carbachol (CCh, 70–100μM) induced: (i) spontaneous and synchronous field oscillations (duration=up to 7s) that were mirrored by intracellular depolarizations with rhythmic action potential bursts; and (ii) depolarizing plateau potentials (DPPs, duration=up to 2.5s) associated with action potential discharge in response to brief (50–100ms) intracellular depolarizing current pulses. Ionotropic glutamatergic receptor antagonists abolished the field oscillations without influencing DPPs, while atropine (1μM) markedly reduced both types of activity. Topiramate (10–100μM, n =8–13 slices) or lamotrigine (50–400μM, n =3–12) decreased in a dose-dependent manner, and eventually abolished, CCh-induced field oscillations. During topiramate application, these effects were accompanied by marked DPP reduction. When these antiepileptic drugs were tested on DPPs recorded in the presence of CCh+ionotropic glutamatergic and GABA receptor antagonists, only topiramate reduced DPPs (n =5–19/dose; IC50 =18μM, n =48). Similar effects were induced by topiramate during metabotropic glutamate receptor antagonism (n =5), which did not influence DPPs. Thus, topiramate and lamotrigine reduce CCh-induced epileptiform synchronization in the rat subiculum but only topiramate is effective in controlling DPPs. We propose that muscarinic receptor-mediated excitation represents a target for the action of some antiepileptic drugs such as topiramate. [Copyright &y& Elsevier]