Palmitoylethanolamide ameliorates neuroinflammation via modulating PPAR-α to promote the functional outcome after intracerebral hemorrhage.

Guoyang Zhou, Xiongjie Fu, Liang Wang, Yang Cao, JianFeng Zhuang, Junwen Hu, Yin Li, Chaoran Xu, Shiqi Gao, Anwen Shao, Lin Wang

Neuroscience letters 2022 Jun 11

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Intracerebral hemorrhage is a type of acute cerebrovascular disease that remains one of the main causes of death and disability. After the onset of ICH, different types of severe pathophysiological changes can cause great damage to brain tissue, including neuroinflammation. Our study demonstrated the effect of PEA on modulating microglia phenotype and neuroinflammation, as well as the possible underlying mechanisms after ICH for the first time. The phenotypic transformation of microglia and simulation of neuroinflammation after ICH in vitro was induced by hemoglobin on BV2 cells. Additionally, the experiment in vivo model was induced by collagenase injection in mice. The role of PEA on hematoma clearance was also discussed. Western blot, ELISA and immunofluorescence staining were used to determine the phenotypic polarization of microglia and neuroinflammation. In order to evaluate the role of PPAR-α in the anti-inflammatory effect of PEA after ICH, the PPAR-α antagonist GW6471 was utilized. Behavior tests examined the effect of PEA on improving neuronal function. Our results showed that PEA can ameliorate neuroinflammation by inhibiting upregulation of NF-κB, IL-1β and TNF-α, both in vivo and in vitro. Additionally, PEA can improve motor function in ICH mice and promotes hematoma clearance. At the same time, PEA can increase the levels of PPAR-α in the nucleus. Hence, PPAR-α antagonists can reverse the protective effects of PEA on neuroinflammation. These results suggest that PEA is involved in microglia polarization, attenuating the activation of neuroinflammation, as well as improving motor function after ICH. This, at least in part, may contribute to the involvement of PPAR-α modulation of NF-κB. Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Citation

Guoyang Zhou, Xiongjie Fu, Liang Wang, Yang Cao, JianFeng Zhuang, Junwen Hu, Yin Li, Chaoran Xu, Shiqi Gao, Anwen Shao, Lin Wang. Palmitoylethanolamide ameliorates neuroinflammation via modulating PPAR-α to promote the functional outcome after intracerebral hemorrhage. Neuroscience letters. 2022 Jun 11;781:136648