title: Effect of midazolam on the proliferation of neural stem cells isolated from rat hippocampus.
abstract: In many recent studies, the inhibitory transmitter gamma-aminobutyric acid has been shown to modulate the proliferation, differentiation and survival of neural stem cells. Most general anesthetics are partial or allosteric gamma-aminobutyric acid A receptor agonists, suggesting that general anesthetics could alter the behavior of neural stem cells. The neuroprotective efficacy of general anesthetics has been recognized for decades, but their effects on the proliferation of neural stem cells have received little attention. This study investigated the potential effect of midazolam, an extensively used general anesthetic and allosteric gamma-aminobutyric acid A receptor agonist, on the proliferation of neural stem cells in vitro and preliminarily explored the underlying mechanism. The proliferation of neural stem cells was tested using both Cell Counting Kit 8 and bromodeoxyuridine incorporation experiments. Cell distribution analysis was performed to describe changes in the cell cycle distribution in response to midazolam. Calcium imaging was employed to explore the molecular signaling pathways activated by midazolam. Midazolam (30-90 μM) decreased the proliferation of neural stem cells in vitro. Pretreatment with the gamma-aminobutyric acid A receptor antagonist bicuculline or Na-K-2Cl cotransport inhibitor furosemide partially rescued this inhibition. In addition, midazolam triggered a calcium influx into neural stem cells. The suppressive effect of midazolam on the proliferation of neural stem cells can be partly attributed to the activation of gamma-aminobutyric acid A receptor. The calcium influx triggered by midazolam may be a trigger factor leading to further downstream events.
authors: Department of Anesthesiology, the General Hospital of Chinese PLA, Beijing 100853, China.
authors: Sanjun
authors: S
authors: Zhao
authors: Department of Obstetrics and Gynecology, Luhe Teaching Hospital, Capital Medical University, Beijing 101100, China.
authors: Yajing
authors: Y
authors: Zhu
authors: Beijing Institute of Pharmacology and Toxicology, Beijing 100853, China.
authors: Rui
authors: R
authors: Xue
authors: Beijing Institute of Pharmacology and Toxicology, Beijing 100853, China.
authors: Yunfeng
authors: Y
authors: Li
authors: The 254 Hospital of Chinese PLA, Tianjin 300142, China.
authors: Hui
authors: H
authors: Lu
authors: Department of Anesthesiology, the General Hospital of Chinese PLA, Beijing 100853, China.
authors: Weidong
authors: W
authors: Mi
keywords: gamma-aminobutyric acid A receptor; general anesthetics; hippocampus; midazolam; nerve injury; neural regeneration; neural stem cells; proliferation
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