2. Academic Validation
  3. Effect of esketamine pretreatment on acute sepsis-associated encephalopathy

Effect of esketamine pretreatment on acute sepsis-associated encephalopathy

  • Exp Neurol. 2023 Dec 7:114646. doi: 10.1016/j.expneurol.2023.114646.
Cong-Mei Wang 1,  Yan Zhang 2,  Yu-Shen Yang 3,  Shu Lin 4,  He-Fan He 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Shishi General Hospital, Fujian Province, China.
  • 2 Department of Anesthesiology, Zhuzhou Central Hospital, Hunan Province, China.
  • 3 Department of Anesthesiology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China.
  • 4 Department of Anesthesiology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China; Group of Neuroendocrinology, Garvan Institute of Medical Research, 384 Victoria St, Sydney, Australia; Center of Neurological and Metabolic Research, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China.
  • 5 Department of Anesthesiology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China. Electronic address: 15860905262@163.com.
PMID: 38070725 DOI: 10.1016/j.expneurol.2023.114646
Abstract

Purpose: Esketamine, the S(+) enantiomer of ketamine, exhibits good anesthetic efficacy and controllability; however, its potential clinical applications, particularly in sepsis-associated encephalopathy (SAE), remain underexplored. SAE involves the development of diffuse brain dysfunction after sepsis, leading to markedly increased sepsis-related disability and mortality. In this study, we investigated the effects of esketamine pretreatment on acute SAE.

Methods: Mice were randomly divided into four groups: control (C, n = 22), acute SAE (L, n = 22), esketamine pretreatment + acute SAE (EL, n = 22), and nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor (ML385) + esketamine pretreatment + acute SAE (N + EL, n = 22). Acute SAE was established using intraperitoneal (i.p.) injection of lipopolysaccharide (LPS; 10 mg/kg), while controls received equal amounts of saline. The EL group received daily i.p. injections of esketamine (10 mg/kg) for 5 consecutive days, followed by LPS on day 6. The N + EL group received i.p. injections of ML385 (30 mg/kg) 1 h before esketamine pretreatment. The remainder of treatment followed the same protocol as the EL group. Behavioral tests were performed 24 h post-LPS injection, and whole blood and brain tissues were collected for further analysis.

Results: Esketamine improved sepsis symptoms, 7-day survival, and spatial cognitive impairment, without altering locomotor activity. Moreover, esketamine reversed the LPS-induced increase in serum S100 calcium-binding protein β and neuron-specific Enolase levels and reduced hippocampal neuroinflammation, oxidative stress, and neuronal Apoptosis in the EL group. However, these neuroprotective effects of esketamine were reversed by ML385.

Conclusion: The results of our study suggest that esketamine pretreatment mitigates acute SAE, highlighting the involvement of the Nrf2/heme oxygenase-1 pathway in mediating its neuroprotective effects.

Keywords

Aepsis-associated encephalopathy; Anesthesia; Apoptosis; Esketamine; Lipopolysaccharide; Neuroinflammation; Nuclear factor erythroid 2-related factor 2; Oxidative stress.

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