4/30/2023 0 Comments Liquid rhythm jbridgeIn view of our previous finding indicating a selective reduction of allopregnanolone levels in the hippocampus of KA-treated rats, in which this neurosteroid was related to the seizure occurrence observed in epileptic animals, we determined whether allopregnanolone and other neurosteroids could be altered after LEV treatment, using liquid chromatography-electrospray-tandem mass spectrometry (LC-ESI-MS/MS). To this aim, kainic acid (KA)-treated rats were first monitored by video-electrocorticographic (v-ECoG) recordings coupled with power band spectrum analysis before, during LEV administration via osmotic minipumps for a week, and subsequently in the weeks following LEV withdrawal. Thus, we decided to use LEV and designed an experiment to fully characterize its therapeutic properties and the consequences of LEV rapid withdrawal. To this regard, LEV appears as an ideal tool to test the rebound effect in a post- status epilepticus model of chronic epilepsy. LEV has the advantage of being water-soluble and thus can be administered without using any solvent potentially able to affect the central nervous system function. These findings suggest a role for the seizure postictal component in the rebound effect, which involves an imbalance of hippocampal neurosteroid levels. Notably, allopregnanolone hippocampal levels were positively related to the seizure occurrence ( r 2 = 0.51, p = 0.02) and to the power of delta band ( r 2 = 0.67, p = 0.004). The power of delta band in the seizure postictal component was related to the seizure occurrence after LEV withdrawal ( r 2 = 0.73, p < 0.001). In the first week of LEV discontinuation, seizures increased abruptly up to 700% ( p = 0.002, Tukey’s test). LEV significantly reduced the percentage of rats experiencing seizures, reduced the seizure duration, and altered cerebral levels of neurosteroids. Furthermore, we assessed endogenous neurosteroid levels by liquid chromatography-electrospray-tandem mass spectrometry. Seizures were evaluated by video-electrocorticographic recordings and power band spectrum analysis. The effects of LEV were determined by comparing time intervals, treatments, and interactions between these main factors. LEV was continuously administered using osmotic minipumps, 7 weeks after the intraperitoneal administration of kainic acid (15 mg/kg). saline, n = 15), we investigated the rebound effect in adult male Sprague-Dawley rats. By stopping treatment with levetiracetam (LEV 300 mg/kg/day, n = 15 vs. Abrupt withdrawal from antiepileptic drugs is followed by increased occurrence of epileptic seizures, a phenomenon known as the “rebound effect”.
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