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Effect of midazolam on the proliferation of neural stem cells isolated from rat hippocampus.

Zhao S, Zhu Y, Xue R, Li Y, Lu H, Mi W - Neural Regen Res (2012)

Bottom Line: 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 calcium influx triggered by midazolam may be a trigger factor leading to further downstream events.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, the General Hospital of Chinese PLA, Beijing 100853, China.

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.

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Calcium imaging in neural stem cells. Calcium-dependent fluorescence was elevated immediately upon administration of 90 μM mid and this effect was completely blocked by pretreatment with 10 μM bic. The images were collected at a frequency of 5 seconds per frame.Data are expressed as mean ± SEM (n = 6). aP < 0.05, vs. veh group and bic + mid group using two-way analysis of variance. T1: Fluorescence intensity at resting state; T2: fluorescence intensity after administration; mid: midazolam; bic: bicuculline; veh: vehicle.
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Figure 5: Calcium imaging in neural stem cells. Calcium-dependent fluorescence was elevated immediately upon administration of 90 μM mid and this effect was completely blocked by pretreatment with 10 μM bic. The images were collected at a frequency of 5 seconds per frame.Data are expressed as mean ± SEM (n = 6). aP < 0.05, vs. veh group and bic + mid group using two-way analysis of variance. T1: Fluorescence intensity at resting state; T2: fluorescence intensity after administration; mid: midazolam; bic: bicuculline; veh: vehicle.

Mentions: To explore the underlying mechanisms mediating the effect of midazolam on neural stem cells, we examined intracellular calcium metabolism using the calcium-sensitive fluorescent dye fluo-3 AM. Midazolam (90 μM) evoked a rapid increase in the intracellular calcium concentration, whereas pretreatment with 10 μM bicuculline almost completely blocked the calcium influx caused by midazolam (Figure 5, supplementary Figure 3 online).


Effect of midazolam on the proliferation of neural stem cells isolated from rat hippocampus.

Zhao S, Zhu Y, Xue R, Li Y, Lu H, Mi W - Neural Regen Res (2012)

Calcium imaging in neural stem cells. Calcium-dependent fluorescence was elevated immediately upon administration of 90 μM mid and this effect was completely blocked by pretreatment with 10 μM bic. The images were collected at a frequency of 5 seconds per frame.Data are expressed as mean ± SEM (n = 6). aP < 0.05, vs. veh group and bic + mid group using two-way analysis of variance. T1: Fluorescence intensity at resting state; T2: fluorescence intensity after administration; mid: midazolam; bic: bicuculline; veh: vehicle.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4308778&req=5

Figure 5: Calcium imaging in neural stem cells. Calcium-dependent fluorescence was elevated immediately upon administration of 90 μM mid and this effect was completely blocked by pretreatment with 10 μM bic. The images were collected at a frequency of 5 seconds per frame.Data are expressed as mean ± SEM (n = 6). aP < 0.05, vs. veh group and bic + mid group using two-way analysis of variance. T1: Fluorescence intensity at resting state; T2: fluorescence intensity after administration; mid: midazolam; bic: bicuculline; veh: vehicle.
Mentions: To explore the underlying mechanisms mediating the effect of midazolam on neural stem cells, we examined intracellular calcium metabolism using the calcium-sensitive fluorescent dye fluo-3 AM. Midazolam (90 μM) evoked a rapid increase in the intracellular calcium concentration, whereas pretreatment with 10 μM bicuculline almost completely blocked the calcium influx caused by midazolam (Figure 5, supplementary Figure 3 online).

Bottom Line: 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 calcium influx triggered by midazolam may be a trigger factor leading to further downstream events.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, the General Hospital of Chinese PLA, Beijing 100853, China.

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.

No MeSH data available.


Related in: MedlinePlus