Dexmedetomidine Ameliorates Postoperative Cognitive Dysfunction in Aged Mice.

Abstract

Neuroinflammation and oxidative stress coexist and interact in the progression of postoperative cognitive dysfunction (POCD) and other neurodegenerative disease. Mounting studies reveal that Dexmedetomidine (Dex) possesses anti-inflammatory and antioxidant properties. Nevertheless, whether Dex exerts neuroprotective effect on the cognitive sequelae of oxidative stress and inflammatory process remains unclear. A mouse model of abdominal exploratory laparotomy-induced cognitive dysfunction was employed to explore the underlying mechanism of neuroprotective effects exerted by Dex in POCD. Aged mice were treated with Dex (20 µg/kg) 20 min prior to surgery. Open field test (OFT) and Morris water maze (MWM) were employed to examine the cognitive function on postoperative day 3 (POD 3) or POD 7. In the present study, mice underwent surgery exhibited cognitive impairment without altering spontaneous locomotor activity, while the surgery-induced cognitive impairment could be alleviated by Dex pretreatment. Dex inhibited surgery-induced pro-inflammatory cytokines accumulation and microglial activation in the hippocampi of mice. Furthermore, Dex decreased MDA levels, enhanced SOD activity, modulated CDK5 activity and increased BDNF expression in the hippocampus. In addition, Dex remarkably reduced the surgery-induced increased ratio of Bax/Bcl-2 and apoptotic neurons in the hippocampi of aged mice. Collectively, our study provides evidence that Dex may exert neuroprotective effects against surgery-induced cognitive impairment through mechanisms involving its anti-inflammatory and antioxidant properties, as well as the suppression on the mitochondrial permeability transition pore and apoptosis-related pathway.

• Authors: Xiaolan Xie, Zhiwen Shen, Chuwen Hu, Kun Zhang, Mingyan Guo, Fei Wang, Kai Qin
• Journal: Neurochemical research (Neurochem Res) Vol. 46 Issue 9 Pg. 2415-2426 (Sep 2021) ISSN: 1573-6903 [Electronic] United States
• PMID: 34159456 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Bdnf protein, mouse
• Brain-Derived Neurotrophic Factor
• Cytokines
• Neuroprotective Agents
• Malondialdehyde
• Dexmedetomidine
• Superoxide Dismutase
• Cyclin-Dependent Kinase 5
• Cdk5 protein, mouse

Topics

• Abdomen (surgery)
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Antioxidants (therapeutic use)
• Brain-Derived Neurotrophic Factor (metabolism)
• Cyclin-Dependent Kinase 5 (metabolism)
• Cytokines (metabolism)
• Dexmedetomidine (therapeutic use)
• Hippocampus (drug effects, metabolism)
• Male
• Malondialdehyde (metabolism)
• Mice, Inbred C57BL
• Microglia (drug effects, metabolism)
• Morris Water Maze Test (drug effects)
• Neuroprotective Agents (therapeutic use)
• Open Field Test (drug effects)
• Postoperative Cognitive Complications (drug therapy, metabolism)
• Superoxide Dismutase (metabolism)