Dexmedetomidine Protects Neural Stem Cells from Ketamine-Induced Injury.

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.

• Authors: Pan Lu, Shan Lei, Weisong Li, Yang Lu, Juan Zheng, Ning Wang, Yongjun Xia, Haixia Lu, Xinlin Chen, Yong Liu, Peng-Bo Zhang
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 47 Issue 4 Pg. 1377-1388 ( 2018) ISSN: 1421-9778 [Electronic] Germany
• PMID: 29929189 (Publication Type: Journal Article)
• Copyright: © 2018 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• Nerve Tissue Proteins
• Dexmedetomidine
• Ketamine

Topics

• Animals
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Dexmedetomidine (pharmacology)
• Ketamine (adverse effects, pharmacology)
• MAP Kinase Signaling System (drug effects)
• Nerve Tissue Proteins (metabolism)
• Neural Stem Cells (metabolism, pathology)
• Rats
• Rats, Sprague-Dawley