Effects of sevoflurane preconditioning on microglia/macrophage dynamics and phagocytosis profile against cerebral ischemia in rats

CNS Neurosci Ther. 2018 Jun;24(6):564-571. doi: 10.1111/cns.12823. Epub 2018 Feb 9.

Abstract

Aim: The effects of sevoflurane on microglia/macrophages, promoting or suppressing their activation, remains controversy. We aimed to determine whether sevoflurane preconditioning can protect brain via changing microglia/macrophage dynamics and phagocytosis profile after ischemia.

Methods: The impact of sevoflurane preconditioning was evaluated on microglia/macrophage migration, phagocytosis and proliferation altogether from day 1 to day 7 after transient middle cerebral arterial occlusion (tMCAO) in rats.

Results: Sevoflurane preconditioning was identified to accelerate microglia/macrophage migrating to and invasion in the ischemic core from day 1 to day 5 after damage. Significant accumulation of amoeboid and phagocytic microglia/macrophages was observed in sevoflurane group from day 3 to day 5 after ischemia injury. In addition, sevoflurane pretreatment also promoted the proliferation of microglia/macrophage (Iba1+ /Ki67+ ) dramatically in ischemic core on day 3 postinsult.

Conclusions: Our current study has identified the impact of sevoflurane preconditioning on microglia/macrophage dynamics, including its migration, phagocytosis, and proliferation at early stage after brain ischemia and reperfusion. Sevoflurane might enhance microglia/macrophage activation and promote brain repair. These results could help to approach more relevant microglia/macrophage cell-based strategy for human stroke therapy.

Keywords: ischemia and reperfusion; microglia/macrophage; migration; phagocytosis; proliferation; sevoflurane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Binding Proteins / metabolism
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / pathology
  • Disease Models, Animal
  • Drug Administration Schedule
  • Infarction, Middle Cerebral Artery / diagnostic imaging
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / pathology
  • Ischemic Preconditioning / methods
  • Macrophages / drug effects*
  • Male
  • Microfilament Proteins / metabolism
  • Microglia / drug effects*
  • Microscopy, Confocal
  • Microtubule-Associated Proteins / metabolism
  • Neuroprotective Agents
  • Phagocytosis / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Sevoflurane / administration & dosage*
  • Time Factors

Substances

  • Aif1 protein, rat
  • Calcium-Binding Proteins
  • MAP2 protein, rat
  • Microfilament Proteins
  • Microtubule-Associated Proteins
  • Neuroprotective Agents
  • Platelet Aggregation Inhibitors
  • Sevoflurane