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Inhibition of microglial activation contributes to propofol‐induced protection against post‐cardiac arrest brain injury in rats
Author(s) -
Wang Wei,
Lu Rui,
Feng Dayun,
Liang Lirong,
Liu Bing,
Zhang Hui
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13179
Subject(s) - microglia , propofol , pharmacology , p38 mitogen activated protein kinases , medicine , neuroinflammation , hippocampal formation , hippocampus , neuroscience , anesthesia , mapk/erk pathway , phosphorylation , biology , inflammation , endocrinology , immunology , microbiology and biotechnology
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 CA 1 region, revealed by increased OX 42 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.