Necrostatin-1 Against Sevoflurane-Induced Cognitive Dysfunction Involves Activation of BDNF/TrkB Pathway and Inhibition of Necroptosis in Aged Rats.

Abstract

Postoperative cognitive dysfunction (POCD) induced by anesthesia or surgery has become a common complication in the aged population. Sevoflurane, a clinical inhalation anesthetic, could stimulate calcium overload and necroptosis to POCD. In addition, necroptosis inhibitor necrostatin-1 (Nec-1) alleviated cognitive impairment caused by multiple causes, including postoperative cognitive impairment. However, whether Nec-1 exerts a neuroprotective effect on POCD via calcium and necroptosis remains unclear. We anesthetized Sprague-Dawley rats with sevoflurane to construct the POCD model and to explore the mechanism underlying neuroprotective effects of Nec-1 in POCD. Rats were treated with Nec-1 (6.25 mg/kg) 1 h prior to anesthesia. Open field test and Morris water maze were employed to detect the cognitive function. In this study, rats exposed to sevoflurane displayed cognitive dysfunction without changes in spontaneous activity; however, the sevoflurane-induced POCD could be relieved by Nec-1 pretreatment. Nec-1 decreased sevoflurane-induced calcium overload and calpain activity in the hippocampus. In addition, Nec-1 alleviated the expression of p-RIPK1, RIPK1, p-RIPK3, RIPK3, p-MLKL and MLKL. Furthermore, Nec-1 remarkably increased BDNF and p-TrkB/TrkB expression in the hippocampus of aged rats. Ultimately, our research manifests evidence that Nec-1 may play a neuroprotective role against sevoflurane-induced cognitive impairment via the increase of BDNF/TrkB and suppression of necroptosis-related pathway.

• Authors: Chunping Yin, Qi Zhang, Juan Zhao, Yanan Li, Jiaxu Yu, Wei Li, Qiujun Wang
• Journal: Neurochemical research (Neurochem Res) Vol. 47 Issue 4 Pg. 1060-1072 (Apr 2022) ISSN: 1573-6903 [Electronic] United States
• PMID: 35040026 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Brain-Derived Neurotrophic Factor
• Imidazoles
• Indoles
• necrostatin-1
• Sevoflurane

Topics

• Animals
• Brain-Derived Neurotrophic Factor (metabolism)
• Cognitive Dysfunction (chemically induced, drug therapy, metabolism)
• Hippocampus (metabolism)
• Imidazoles
• Indoles
• Necroptosis
• Rats
• Rats, Sprague-Dawley
• Sevoflurane (adverse effects)