Mechanisms of Action of Propofol in Modulating Microglial Activation in Ischemic Stroke

Abstract

Ischemic stroke, responsible for the majority of stroke cases worldwide, triggers profound neuroinflammatory responses largely mediated by microglia. Excessive activation of pro-inflammatory microglia exacerbates neuronal injury, highlighting the need for therapeutic strategies targeting microglial modulation. Propofol (2,6-diisopropylphenol), a widely used intravenous anesthetic, has emerged as a promising neuroprotective agent due to its potent anti-inflammatory properties. This review comprehensively explores the diverse cellular mechanisms by which propofol attenuates microglial activation and inflammation in ischemic stroke. By elucidating these molecular pathways, it underscores the therapeutic potential of propofol in mitigating ischemic brain injury and guiding future clinical interventions.

Keywords: inflammation; microglia; propofol; stroke.

Figure 1

A comprehensive depiction of the cellular mechanisms through which propofol attenuates microglial activation and neuroinflammation in the context of ischemic stroke. Propofol exerts its neuroprotective effects via multiple molecular targets and signaling pathways, including the modulation of the PI3K/Akt cascade, inhibition of NOX, downregulation of TLR4 and Cx43, and activation of the JAK1/STAT3 pathway. It also regulates miRNA-mediated signaling, particularly the miR-155/SOCS1 and miR-221/222–IRF2 axes. Additional mechanisms include the suppression of the NF-κB/HIF-1α pathways, reduction in EV release, attenuation of oxidative stress via decreased ROS, and maintenance of intracellular Ca²⁺ homeostasis. Created with BioRender.com (URL accessed on 25 April 2025).