Neuroprotective Effects of Dexmedetomidine on the Ketamine-Induced Disruption of the Proliferation and Differentiation of Developing Neural Stem Cells in the Subventricular Zone

Frontiers in Pediatrics

article

Huanhuan Sha¹  Peipei Peng¹  Guohua Wei¹  Juan Wang¹  Yuqing Wu²  He Huang¹ 

[1] Department of Anesthesiology and Perioperative Medicine, First Affiliated Hospital of Nanjing Medical University;Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University

关键词: dexmedetomidine;    neural stem cells;    subventricular zone;    neuroprotection;    ketamine;    olfactory cognitive function;   

DOI  :  10.3389/fped.2021.649284

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Background: Ketamine disrupts the proliferation and differentiation of developing neural stem cells (NSCs). Therefore, the safe use of ketamine in pediatric anesthesia has been an issue of increasing concern among anesthesiologists and children's parents. Dexmedetomidine (DEX) is widely used in sedation as an antianxiety agent and for analgesia. DEX has recently been shown to provide neuroprotection against anesthetic-induced neurotoxicity in the developing brain. The aim of this in vivo study was to investigate whether DEX exerted neuroprotective effects on the proliferation and differentiation of NSCs in the subventricular zone (SVZ) following neonatal ketamine exposure. Methods: Postnatal day 7 (PND-7) male Sprague-Dawley rats were equally divided into the following five groups: control group ( n = 8), ketamine group ( n = 8), 1 μg/kg DEX+ketamine group ( n = 8), 5 μg/kg DEX+ketamine group ( n = 8) and 10 μg/kg DEX+ketamine group ( n = 8). Immediately after treatment, rats received a single intraperitoneal injection of BrdU, and the proliferation and differentiation of NSCs in the SVZ were assessed using immunostaining at 24 h after the BrdU injection. In the olfactory behavioral tests, rats in each group were raised until 2 months old, and the buried food test and olfactory memory test were performed. Results: The proliferation of NSCs and astrocytic differentiation in the SVZ were significantly inhibited at 24 h after repeated ketamine exposure in the neonatal period, and neuronal differentiation was markedly increased. Furthermore, pretreatment with moderately high (5 μg/kg) or high doses (10 μg/kg) of DEX reversed ketamine-induced disturbances in the proliferation and differentiation of NSCs. In the behavior tests, repeated neonatal ketamine exposure induced olfactory cognitive dysfunction in the adult stage, and moderately high and high doses of DEX reversed the olfactory cognitive dysfunction induced by ketamine. Conclusions: Based on the present findings, pretreatment with a moderately high (5 μg/kg) or high dose (10 μg/kg) of DEX may alleviate the developmental neurogenesis disorder in the SVZ at 24 h after repeated ketamine exposure and improve olfactory cognitive dysfunction in adulthood.

【 授权许可】

CC BY