Abstract
The administration of lithium–pilocarpine (LiPilo) in adult rats is a validated model reproducing the main clinical and neuropathological features of temporal lobe epilepsy (TLE). Previous studies have shown that carisbamate (CRS) has the property of modifying epileptogenesis in this model. When treated with CRS, about 50% of rats undergoing LiPilo status epilepticus (SE) develop non-convulsive seizures (NCS) instead of convulsive ones (commonly observed in TLE). The goal of this work was to determine some of the early changes that occur after CRS administration, as they could be involved in the insult- and epileptogenesis-modifying effects of CRS. Thus, we performed high-performance liquid chromatography (HPLC) to quantify levels of amino acids and monoamines, and c-Fos immunohistochemical labeling to map cerebral activation during seizures. Comparing rats treated one hour after SE onset with saline (CT), CRS, or diazepam (DZP), HPLC showed that 4 h after SE onset, dopamine (DA), norepinephrine (NE), and GABA levels were normal, whereas serotonin levels were increased. Using c-Fos labeling, we demonstrated increased activity in thalamic mediodorsal (MD) and laterodorsal (LD) nuclei in rats treated with CRS. In summary, at early times, CRS seems to modulate excitability by acting on some monoamine levels and increasing activity of MD and LD thalamic nuclei, suggesting a possible involvement of these nuclei in insult- and/or epileptogenesis-modifying effects of CRS.
Highlights
Temporal lobe epilepsy (TLE) is characterized by recurrent spontaneous convulsive seizures [1] that are associated with significant neuronal loss and morphological alterations affecting mainly mesial temporal structures such as the hippocampal formation and amygdala [1,2,3]
Hippocampus: The concentrations of monoamines and amino acids in the hippocampus of rats from control (CT), diazepam (DZP), and CRS groups are shown in Table 1, Figure 2, and Supplementary Figures S2–S4
Our results point to a significant increase in the levels of gamma-aminobutyric acid (GABA) and glutamine (GLN) in the DZP group as compared to CT rats (Figure 2A,C)
Summary
Temporal lobe epilepsy (TLE) is characterized by recurrent spontaneous convulsive seizures [1] that are associated with significant neuronal loss and morphological alterations affecting mainly mesial temporal structures such as the hippocampal formation and amygdala [1,2,3]. The pilocarpine-induced epilepsy model reproduces the main clinical and pathophysiological features of human TLE, i.e., hippocampal sclerosis, cell dispersion in the dentate gyrus, mossy fiber sprouting, and gliosis [4,5]. In this model, an initial phase of status epilepticus (SE) is followed by a latent period lasting 7–44 days, daylesa, dleiandgintog tthoethoeccoucrcruernrceenocef sopfosnptoannteaonueos urescruercruernrtenmtomtoortosreiszeuizreusre[4s][.4I]n. Isnt[e1r1e,s1t2in].gly, Intemreossttinragtlsyt,rmeaotesdt rwatisthtrCeRatSedthawtiltahteCrRdSevtehlaotplaNteCrSdsehvoewloap rNedCuSctsihoonwofaepreildeupctitfioornmoef veepniltespdtuifroirnmg SE eveantt2s–d3uhrianfgteSrECaRtS2a–d3mh ianfitsetrraCtRioSn,aid.em.,iantis4t–ra5thioanf,tei.re.S, Eato4n–s5eth[1a0ft]e.r SE onset [10]
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