title: 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-α and interleukin-1β. In addition, propofol protected neurons from injury when co-culturing with ATP-treated microglia. Our data suggest that propofol pre-treatment inhibits CA-induced microglial activation and neuronal injury in the hippocampus and ultimately improves cognitive function. We proposed a possible mechanism of propofol-mediated brain protection after cardiac arrest (CA). CA induces P2X7R upregulation and p38 phosphorylation in microglia, which induces release of TNF-α and IL-1β and consequent neuronal injury. Propofol could inhibit microglial activation and alleviate neuronal damage. Our results suggest propofol-induced anti-inflammatory treatment as a plausible strategy for therapeutic intervention in post-CA brain injury.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Anesthesiology, School of Stomatology, the Fourth Military Medical University, Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Anesthesiology, School of Stomatology, the Fourth Military Medical University, Xi'an, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: Da-Yun
authors.initials: DY
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Anesthesiology, School of Stomatology, the Fourth Military Medical University, Xi'an, China.
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Anesthesiology, School of Stomatology, the Fourth Military Medical University, Xi'an, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Anesthesiology, School of Stomatology, the Fourth Military Medical University, Xi'an, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001237:Asphyxia / Q000150:complications; D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology*; D039481:CD11b Antigen / Q000096:biosynthesis / Q000235:genetics; D016887:Cardiopulmonary Resuscitation; D002478:Cells, Cultured; D006323:Heart Arrest / Q000150:complications*; D053583:Interleukin-1beta / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D018782:Maze Learning; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use; D023421:Models, Animal; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation; D015742:Propofol / Q000494:pharmacology / Q000627:therapeutic use*; D011499:Protein Processing, Post-Translational; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D053583:Interleukin-1beta; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D058486:Receptors, Purinergic P2X7; D014409:Tumor Necrosis Factor-alpha; D000255:Adenosine Triphosphate; D048051:p38 Mitogen-Activated Protein Kinases; D008911:Minocycline; D015742:Propofol
keywords: cardiac arrest; cardiopulmonary resuscitation; hippocampus; microglia; propofol