Abstract
BackgroundTemporal lobe epilepsy (TLE) is the most common form of partial epilepsy and is accompanied, in one third of cases, by resistance to antiepileptic drugs (AED). Most AED target neuronal activity modulated by ionic channels, and the steroid sensitivity of these channels has supported the use of corticosteroids as adjunctives to AED. Assuming the importance of astrocytes in neuronal activity, we investigated inflammatory and astroglial markers in the hippocampus, a key structure affected in TLE and in the Li-pilocarpine model of epilepsy.MethodsInitially, hippocampal slices were obtained from sham rats and rats subjected to the Li-pilocarpine model of epilepsy, at 1, 14, and 56 days after status epilepticus (SE), which correspond to the acute, silent, and chronic phases. Dexamethasone was added to the incubation medium to evaluate the secretion of S100B, an astrocyte-derived protein widely used as a marker of brain injury. In the second set of experiments, we evaluated the in vivo effect of dexamethasone, administrated at 2 days after SE, on hippocampal inflammatory (COX-1/2, PGE2, and cytokines) and astroglial parameters: GFAP, S100B, glutamine synthetase (GS) and water (AQP-4), and K+ (Kir 4.1) channels.ResultsBasal S100B secretion and S100B secretion in high-K+ medium did not differ at 1, 14, and 56 days for the hippocampal slices from epileptic rats, in contrast to sham animal slices, where high-K+ medium decreased S100B secretion. Dexamethasone addition to the incubation medium per se induced a decrease in S100B secretion in sham and epileptic rats (1 and 56 days after SE induction). Following in vivo dexamethasone administration, inflammatory improvements were observed, astrogliosis was prevented (based on GFAP and S100B content), and astroglial dysfunction was partially abrogated (based on Kir 4.1 protein and GSH content). The GS decrease was not prevented by dexamethasone, and AQP-4 was not altered in this epileptic model.ConclusionsChanges in astroglial parameters emphasize the importance of these cells for understanding alterations and mechanisms of epileptic disorders in this model. In vivo dexamethasone administration prevented most of the parameters analyzed, reinforcing the importance of anti-inflammatory steroid therapy in the Li-pilocarpine model and possibly in other epileptic conditions in which neuroinflammation is present.
Highlights
Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and is accompanied, in one third of cases, by resistance to antiepileptic drugs (AED)
Dexamethasone prevents the decrease in glutathione in the Li-pilocarpine model of epilepsy Based on the astrogliosis signals found in this model, we investigated other astroglial parameters related to astrocyte functionality, namely, glutamine synthetase (GS) activity, Reduced glutathione (GSH) content, potassium channel Kir 4.1, and aquaporin-4 (AQP-4)
Our results indicate a decrease in neuroinflammation, astrogliosis, and astroglial dysfunction in the hippocampi of young rats submitted to the Li-pilocarpine model of epilepsy, at 1 and 56 days after intraperitoneal dexamethasone administration
Summary
Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and is accompanied, in one third of cases, by resistance to antiepileptic drugs (AED). Temporal lobe epilepsy (TLE) that affects the limbic system [5, 6] is the most common form of partial epilepsy and resistance to anticonvulsive drugs which develops in about 30% of cases [7, 8]. Astrogliosis and neuroinflammation have been correlated to epileptogenesis, recurrent, and spontaneous seizures [24,25,26,27,28,29] For this reason, specific astroglial targets (e.g., S100B, glutamine synthetase (GS), potassium channel Kir 4.1, and water channel AQP-4) have been investigated with a view to improving therapeutic approaches and the development of antiepileptic drugs [30]
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