DFP-Induced Status Epilepticus Severity in Mixed-Sex Cohorts of Adult Rats Housed in the Same Room: Behavioral and EEG Comparisons.
DFP-Induced Status Epilepticus Severity in Mixed-Sex Cohorts of Adult Rats Housed in the Same Room: Behavioral and EEG Comparisons.
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DOI：
10.3389/fcell.2022.895092
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发表时间：
2022
影响因子：
5.5
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性别是实验模型中的一个生物学变量。在我们之前的二异丙基氟磷酸盐 (DFP) 研究中，雌性大鼠需要更高剂量的 DFP 才能达到与雄性大鼠相似的癫痫持续状态 (SE) 严重程度。在这些研究中，雄性和雌性大鼠分别从同一供应商处购买，饲养在不同的房间，并且使用的DFP来自不同批次。我们还表明，硬膜外电极植入手术可降低 SE 的阈值。我们最近对索曼 (GD) 模型进行的研究使用了单独饲养但在同一房间的混合性别大鼠队列，结果表明，在相同剂量的 GD 下，雌性的 SE 严重程度明显高于雄性。在这项研究中，我们证明，将混合性别群体安置在同一房间，并使用同一池中不同批次的 DFP（4 mg/kg，皮下注射）进行治疗，在两性以及遥测（手术）和非遥测（非手术）组中均产生了可重复的 SE 严重程度。我们对四个混合性别的成年斯普拉格-道利大鼠进行了实验。在女性中，与非遥测女性相比，植入遥测设备的手术减少了惊厥性癫痫发作 (CS) 的潜伏期，并增加了 SE 的严重程度。然而，遥测组或非遥测组中的潜伏期或 SE 严重程度没有性别差异。一旦动物达到CS阶段≥3，它们在雌性和雌性中都保持在CS阶段，直到给予咪达唑仑。 DFP 后 1 小时给予咪达唑仑（3 mg/kg，肌肉注射）治疗可显着降低男女癫痫样峰值。 24 小时内死亡率仅为 2%。无论性别、动情周期或手术阶段如何，动物都会出现持续惊厥性 SE 约 40 分钟。在遥测大鼠中，电图变化与行为癫痫发作相关。然而，两性的直接观察行为 CS 和基于脑电图的 CS 量化之间的 SE 严重程度和潜伏期存在显着差异。总体而言，这些结果表明，将两性安置在同一房间并在混合性别队列中使用同一试剂池中的 DFP 进行治疗将最大限度地减少 SE 严重程度的变异性。在癫痫模型中测试疾病缓解剂时，这种严格的实验将产生更好的结果。
Sex is a biological variable in experimental models. In our previous diisopropylfluorophosphate (DFP) studies, female rats required a higher dose of DFP to achieve a somewhat similar severity of status epilepticus (SE) as males. In those studies, male and female rats were bought separately from the same vendor, housed in different rooms, and the DFP used was from different batches. We had also shown that surgery for epidural electrodes implantation reduces the threshold for SE. Our recent study in the soman (GD) model using a mixed-sex cohort of rats housed individually but in the same room showed that females achieved significantly higher SE severity than males for the same dose of GD. In this study, we demonstrate that housing the mixed-sex cohorts in the same room and treating them with DFP (4 mg/kg, s.c.) from the same pool, though from different batches, yielded reproducible SE severity in both sexes and both telemetry (surgery) and non-telemetry (non-surgery) groups. We conducted experiments in four mixed-sex cohorts of adult Sprague-Dawley rats. In females, the surgery for implanting the telemetry devices reduced the latency to convulsive seizure (CS) and increased SE severity compared to non-telemetry females. However, there were no sex differences in latency or SE severity within telemetry or non-telemetry groups. Once animals reached CS stage ≥3, they remained in CS stage in both sexes until midazolam was administered. Midazolam (3 mg/kg, i.m.) treatment 1-one-hour post-DFP significantly reduced epileptiform spikes in both sexes. The mortality was only 2% in 24 h. Irrespective of sex or stage of estrous cycle or surgery, the animals had continuous convulsive SE for ∼40 min. In telemetry rats, electrographic changes correlated with behavioral seizures. However, there was a significant difference in SE severity and the latency between directly-observed behavioral CS and EEG-based CS quantification in both sexes. Overall, these results suggest that housing both sexes in the same room and treating with DFP in a mixed-sex cohort from the same pool of reagents will minimize variability in SE severity. Such rigorous experiments will yield better outcomes while testing disease-modifying agents in epilepsy models.