Inhibition of microglial activation contributes to propofol‐induced protection against post‐cardiac arrest brain injury in rats

Abstract

It has been suggested that propofol can modulate microglial activity and hence may have potential roles against neuroinflammation following brain ischemic insult. However, whether and how propofol can inhibit post-cardiac arrest brain injury via inhibition of microglia activation remains unclear. A rat model of asphyxia cardiac arrest (CA) was created followed by cardiopulmonary resuscitation. CA induced marked microglial activation in the hippocampal CA1 region, revealed by increased OX42 and P2 class of purinoceptor 7 (P2X7R) expression, as well as p38 MAPK phosphorylation. Morris water maze showed that learning and memory deficits following CA could be inhibited or alleviated by pre-treatment with the microglial inhibitor minocycline or propofol. Microglial activation was significantly suppressed likely via the P2X7R/ p-p38 pathway by propofol. Moreover, hippocampal neuronal injuries after CA were remarkably attenuated by propofol. In vitro experiment showed that propofol pre-treatment inhibited ATP-induced microglial activation and release of tumor necrosis factor-a and interleukin-1b. In addition, propofol protected neurons from injury when co-culturing with ATPtreated microglia. Our data suggest that propofol pre-treatment inhibits CA-induced microglial activation and neuronal injury in the hippocampus and ultimately improves cognitive function.

Store-Operated Ca2+ Entry (SOCE) and Purinergic Receptor-Mediated Ca2+ Homeostasis in Murine bv2 Microglia Cells: Early Cellular Responses to ATP-Mediated Microglia Activation

“…The broad-spectrum tetracycline antibiotic, minocycline, is a known microglia activation inhibitor (Wang W. et al, 2015), with inhibitory action on P2X4 and P2X7 receptors (Stebbing, unpublished observations). To further explore its mechanisms of action on purinergic receptor activation and Ca 2+ homeostasis, we performed two-photon Ca 2+ fluorescence experiments in the presence of 0.1 mM minocycline and varying ATP concentrations.…”

Rostral ventromedial medulla‐mediated descending facilitation following P2X7 receptor activation is involved in the development of chronic post‐operative pain

“…; Wang et al . ), which then induce the dysfunction of serotoninergic neurons in the RVM. These results, together with those of other studies, indicate that cytokines and ROS subsequent to P2X7R activation in microglia can increase the activity of the pain facilitatory ON cells that express 5‐HT in the RVM by changing the environment in which these neurons live and promoting 5‐HT release into the spinal cord.…”

“…P2X7R agonist, the NADPH oxidase activator, or IL-1b induced 5-HT release in the spinal dorsal horn. It was demonstrated that P2X7R activation in microglia triggers the release of proinflammatory mediators, namely, interleukin 1 (IL-1), TNF-a, and ROS (Solle et al 2001;Kim et al 2007;Sperlagh et al 2007;Ying et al 2014;Wang et al 2015), which then induce the dysfunction of serotoninergic neurons in the RVM. These results, together with those of other studies, indicate that cytokines and ROS subsequent to P2X7R activation in microglia can increase the activity of the pain facilitatory ON cells that express 5-HT in the RVM by changing the environment in which these neurons live and promoting 5-HT release into the spinal cord.…”

Anesthesia in Experimental Stroke Research

“…Nevertheless, ketamine is protective against ischemia in vitro as well [103], suggesting potential temperature independent effects. Propofol decreases CMR and CBF, but also offers other properties including mitigation of oxidative and excitotoxic stress [104, 105], apoptosis [106], inflammation [107], and autophagy [108]. Results of preclinical efficacy studies have been mixed.…”