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Neuroprotective Effects of BHDPC, a Novel Neuroprotectant, on Experimental Stroke by Modulating Microglia Polarization
Chuwen Li1,2; Yaqi Bian2; Yu Feng2; Fan Tang2; Liang Wang2; Maggie Pui Man Hoi2; Dan Ma3; Chao Zhao3; Simon Ming Yuen Lee2
2019-05
Source PublicationACS CHEMICAL NEUROSCIENCE
ISSN1948-7193
Volume10Issue:5Pages:2434-2449
Abstract

This study mainly investigated the therapeutic effects of BHDPC on ischemic stroke and its underlying mechanisms. In vivo, the transient middle cerebral artery occlusion (MCAO) was used to induce ischemic model. In vitro, oxygen and glucose deprivation/reperfusion (OGD/R)-induced ischemic stroke in BV-2 microglia and primary neurons, and bEnd.3 mouse cerebral microvascular endothelial cells (ECs) were also used. First, we found that BHDPC exerts considerable neuroprotection against MCAO-induced ischemic injury to mice via alleviating neurological deficits and brain infarcts, inhibiting neuronal cell loss and apoptosis, and attenuating blood brain barrier disruption and tight junction protein changes. Next, we observed that BHDPC significantly reduced microglial M1 activation but enhanced M2 polarization in MCAO-induced ischemic brain. Further experiments in vitro indicated that BHDPC suppressed microglial activation but promoted M2 microglial polarization in OGD/R-induced BV-2 microglia. In addition, conditioned medium (CM) experiments showed that CM from BHDPC-treated BV-2 microglia provided protections against OGD/R-induced ischemic damage in primary neurons and bEnd.3 ECs. Moreover, we found that BHDPC actions on microglial inflammation were associated with the inactivation of NF-kappa B signaling. Interestingly, we also found that BHDPC enhanced phosphorylation of protein kinase A (PKA) and cAMP-response element-binding protein (CREB). The pharmacological inhibition or gene knockdown of PKA/CREB signaling diminished BHDPC-promoted microglial M2 polarization. In summary, BHDPC conferred neuroprotection against ischemic injury in experimental stroke models. Modulating microglial activation and polarization contributes to BHDPC-mediated neuroprotective actions, which in part were mediated by nuclear factor kappa B and PKA/CREB signaling pathway.

KeywordBhdpc Ischemic Stroke Microglia Nf-κb Creb Pka
DOI10.1021/acschemneuro.8b00713
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Neurosciences & Neurology
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Medicinal ; Neurosciences
WOS IDWOS:000468369500034
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Cited Times [WOS]:4   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University,Guangzhou 510182, China
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau999078, China
3.Department of Clinical Neurosciences, Wellcome Trust-MRC Cambridge Stem Cell Institute, University of Cambridge, CambridgeCB2 0AH, U.K
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Chuwen Li,Yaqi Bian,Yu Feng,et al. Neuroprotective Effects of BHDPC, a Novel Neuroprotectant, on Experimental Stroke by Modulating Microglia Polarization[J]. ACS CHEMICAL NEUROSCIENCE,2019,10(5):2434-2449.
APA Chuwen Li.,Yaqi Bian.,Yu Feng.,Fan Tang.,Liang Wang.,...&Simon Ming Yuen Lee.(2019).Neuroprotective Effects of BHDPC, a Novel Neuroprotectant, on Experimental Stroke by Modulating Microglia Polarization.ACS CHEMICAL NEUROSCIENCE,10(5),2434-2449.
MLA Chuwen Li,et al."Neuroprotective Effects of BHDPC, a Novel Neuroprotectant, on Experimental Stroke by Modulating Microglia Polarization".ACS CHEMICAL NEUROSCIENCE 10.5(2019):2434-2449.
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