Pan Lu1, Shan Lei1, Weisong Li1, Yang Lu1, Juan Zheng1, Ning Wang1, Yongjun Xia1,2, Haixia Lu3, Xinlin Chen3, Yong Liu3, Peng-Bo Zhang1. 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.
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: Jeffrey T Young; Roza M Vlasova; Brittany R Howell; Rebecca C Knickmeyer; Elyse Morin; Kaela I Kuitchoua; Gabriele R Lubach; Jean Noel; Xiaoping Hu; Yundi Shi; Gibson Caudill; Andrew L Alexander; Marc Niethammer; Merle G Paule; Christopher L Coe; Mar Sanchez; Martin Styner Journal: Br J Anaesth Date: 2021-02-03 Impact factor: 11.719