Involvement of Nrf-2/HO-1 pathway in sevoflurane-induced cognitive improvement in rats with traumatic brain injury

Behav Brain Res. 2021 May 7:405:113200. doi: 10.1016/j.bbr.2021.113200. Epub 2021 Feb 23.

Abstract

Traumatic brain injury (TBI) is an increasingly common emergency disease that usually leads to prolonged physical and cognitive impairments. In this study, we investigated if sevoflurane could induce cognitive improvement in TBI rats. Rats were subjected to head trauma induced by a fluid percussion device. A two-hour exposure to 3% sevoflurane was performed in a chamber immediately after TBI. Sevoflurane inhalation reduced the neurological and cognitive deficits induced by TBI with ameliorated synaptic injuries in the hippocampus. Moreover, after sevoflurane treatment, the expression of nuclear factor erythroid-2-related factor-2 (Nrf-2) and hemeoxygenase-1 (HO-1) in the hippocampus was enhanced 1 d after TBI and maintained at high levels 14 days later, and oxidative stress induced by TBI was inhibited. However, the HO-1 inhibitor, Zinc protoporphyrin (ZnPP), used to demonstrate the involvement of HO-1, suppressed the protective effect of sevoflurane. These results indicate that sevoflurane administered immediately after TBI may protect against TBI-induced synaptic and cognitive impairments by promoting the antioxidant Nrf-2/HO-1 pathway. Sevoflurane may be a promising anesthetic for patients with TBI.

Keywords: Cognition; Heme oxygenase-1; Nuclear factor erythroid-2-related factor-2; Sevoflurane; Traumatic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Inhalation / administration & dosage
  • Anesthetics, Inhalation / pharmacology*
  • Animals
  • Behavior, Animal / drug effects
  • Brain Injuries, Traumatic / complications*
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / etiology
  • Disease Models, Animal
  • Heme Oxygenase (Decyclizing) / drug effects*
  • Male
  • NF-E2-Related Factor 2 / drug effects*
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Sevoflurane / administration & dosage
  • Sevoflurane / pharmacology*
  • Signal Transduction / drug effects*

Substances

  • Anesthetics, Inhalation
  • NF-E2-Related Factor 2
  • Neuroprotective Agents
  • Nfe2l2 protein, rat
  • Sevoflurane
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat