Molecular Brain (2018-02-01)

Resolvin D2 protects against cerebral ischemia/reperfusion injury in rats

  • Gang Zuo,
  • Dongping Zhang,
  • Rutao Mu,
  • Haitao Shen,
  • Xiang Li,
  • Zhong Wang,
  • Haiying Li,
  • Gang Chen

DOI
https://doi.org/10.1186/s13041-018-0351-1
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 13

Abstract

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Abstract Cerebral ischemia/reperfusion (I/R) injury is a critical factor leading to a poor prognosis for ischemic stroke patients. ω-3 fatty acid supplements taken as part of a daily diet have been shown to improve the prognosis of patients with ischemic stroke. In this study, we aimed to investigate the potential effects of resolvin D2 (RvD2), a derivative of ω-3 fatty acids, and its possible advantage on cerebral I/R injury in rats. Cerebral I/R caused by middle cerebral artery occlusion and reperfusion (MCAO/R) was established in Sprague-Dawley rats. First, in rats fed a regular diet, the MCAO/R stimulus led to a significant decrease in endogenous production of RvD2. Exogenous supply of RvD2 via intraperitoneal injection reversed MCAO/R-induced brain injury, including infarction, inflammatory response, brain edema, and neurological dysfunction. Meanwhile, RvD2 reversed the MCAO/R-induced decrease in the protein level of GPR18, which has been identified as a receptor for RvD2, especially in neurons and brain microvascular endothelial cells (BMVECs). Furthermore, RvD2 exerted rescue effects on MCAO/R-induced neuron and BMVEC death. Moreover, GPR18 antagonist O-1918 could block the rescue effects of RvD2, possibly at least partially though the GPR18-ERK1/2-NOS signaling pathway. Finally, compared with ω-3 fatty acid supplements, RvD2 treatment had a better rescue effect on cerebral infarction, which may be due to the MCAO/R-induced decrease in 5-lipoxygense phosphorylation and subsequent RvD2 generation. In conclusion, compared with ω-3 fatty acids, RvD2 may be an optimal alternative and complementary treatment for ischemic stroke patients with recanalization treatment.

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