Research Institute, Nozaki Tokushukai Hospital, Daito-city, Osaka, Japan.
Department of Anatomy, School of Medicine, International University of Health and Welfare, Narita, Chiba, Japan.
PLoS One. 2022 Aug 19;17(8):e0273219. doi: 10.1371/journal.pone.0273219. eCollection 2022.
At therapeutic concentrations, propofol (PPF), an anesthetic agent, significantly elevates intracellular calcium concentration ([Ca2 +]i) and induces neural death during the developmental period. Preconditioning enables specialized tissues to tolerate major insults better compared with tissues that have already been exposed to sublethal insults. Here, we investigated whether the neurotoxicity induced by clinical concentrations of PPF could be alleviated by prior exposure to sublethal amounts of PPF. Cortical neurons from embryonic day (E) 17 Wistar rat fetuses were cultured in vitro, and on day in vitro (DIV) 2, the cells were preconditioned by exposure to PPF (PPF-PC) at either 100 nM or 1 μM for 24 h. For morphological observations, cells were exposed to clinical concentrations of PPF (10 μM or 100 μM) for 24 h and the survival ratio (SR) was calculated. Calcium imaging revealed significant PPF-induced [Ca2+]i elevation in cells on DIV 4 regardless of PPF-PC. Additionally, PPF-PC did not alleviate neural cell death induced by PPF under any condition. Our findings indicate that PPF-PC does not alleviate PPF-induced neurotoxicity during the developmental period.
在治疗浓度下，麻醉剂丙泊酚（PPF）会显著提高细胞内钙离子浓度([Ca2+]i)，并在发育期间诱导神经细胞死亡。预处理使专门的组织能够更好地耐受主要损伤，而已经暴露于亚致死损伤的组织则不能。在这里，我们研究了临床浓度的 PPF 是否可以通过预先暴露于亚致死剂量的 PPF 来减轻其诱导的神经毒性。从胚胎期 (E) 17 天 Wistar 大鼠胎鼠中培养皮质神经元，并在体外培养第 2 天 (DIV) 时，将细胞用 100 nM 或 1 μM 的 PPF 预处理 24 h（PPF-PC）。为了进行形态观察，将细胞用临床浓度的 PPF（10 μM 或 100 μM）处理 24 h，并计算存活率 (SR)。钙成像显示，无论 PPF-PC 如何，在 DIV 4 时 PPF 都会引起明显的 [Ca2+]i 升高。此外，在任何条件下，PPF-PC 均不能减轻 PPF 诱导的神经细胞死亡。我们的研究结果表明，在发育期间，PPF-PC 不能减轻 PPF 诱导的神经毒性。
