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Cell Physiol Biochem. 2018;47(4):1377-1388. doi: 10.1159/000490823. Epub 2018 Jun 19.

Dexmedetomidine Protects Neural Stem Cells from Ketamine-Induced Injury.

Author information

1
Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
2
Department of Anesthesiology, Affiliated Hospital of Chinese People's Armed Police Engineering University, Xi'an, China.
3
Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University, Xi'an, China.

Abstract

BACKGROUND/AIMS:

Ketamine inhibits the proliferation of neural stem cells (NSCs) and disturbs normal neurogenesis. Dexmedetomidine provides neuroprotection against volatile anesthetic-induced neuroapoptosis and cognitive impairment in the developing brain. Whether it may protect NSCs from ketamine-induced injury remains unknown. In this study, we investigated the protective effects of dexmedetomidine on ketamine-exposed NSCs and explored the mechanisms potentially involved.

METHODS:

Primary NSC cultures were characterized using immunofluorescence. Cell viability was determined using a Cell Counting Kit 8 assay. Proliferation and apoptosis were assessed with BrdU incorporation and TUNEL assays, respectively. Protein levels of cleaved caspase-3, phosphorylated protein kinase B (p-Akt), and glycogen synthase kinase-3β (p-GSK-3β) were quantified using western blotting.

RESULTS:

Ket-amine significantly decreased NSC viability and proliferation and increased their apoptosis. Dexmedetomidine increased NSC proliferation and decreased their apoptosis in a dose-dependent manner. Furthermore, dexmedetomidine pretreatment notably augmented the viability and proliferation of ketamine-exposed NSCs and reduced their apoptosis. Moreover, dexmedetomidine lessened caspase-3 activation and increased p-Akt and p-GSK-3β levels in NSCs exposed to ketamine. The protective effects of dexmedetomidine on ketamine-exposed NSCs could be partly reversed by the PI3K inhibitor LY294002.

CONCLUSIONS:

Collectively, these findings indicate that dexmedetomidine may protect NSCs from ketamine-induced injury via the PI3K/Akt/GSK-3β signaling pathway.

KEYWORDS:

Dexmedetomidine; Ketamine; Neural stem cells; Neurotoxicity; PI3K/Akt/GSK-3β pathway

PMID:
29929189
DOI:
10.1159/000490823
[Indexed for MEDLINE]
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