Cryptotanshinone reduces neurotoxicity induced by cerebral ischemia-reperfusion injury involving modulation of microglial polarization.

IF 1.9 4区医学 Q4 NEUROSCIENCES Restorative neurology and neuroscience Pub Date : 2021-01-01 DOI:10.3233/RNN-201070

Yanfang Mao, Yang Qu, Qingdong Wang

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引用次数: 10

Abstract

Background: The diterpenoid cryptotanshinone (CTS) has wide biological functions, including inhibition of tumor growth, inflammation and apoptosis. The present study aimed to explore the possible effect of CTS on cerebral ischemia/reperfusion (I/R) injury and the underlying mechanisms.

Methods: Male C57BL/6J mice underwent transient middle cerebral artery occlusion (tMCAO) and murine microglia BV2 cells were challenged by Oxygen/glucose deprivation, to mimic I/R and ischemic/hypoxic and reperfusion (H/R) injury, respectively. CTS was administered 0.5 h (10 mg/kg) after the onset of MCAO or 2 h (20μM) post OGD. Infarct volume and neurological deficit were measured. Immunofluorescence, qPCR, and western blot, were performed to detect the expression of cytokines, apoptotic marker, and M1/M2 phenotype-specific genes. Flow cytometry was applied for M1/M2 subpopulation or Annexin V/PI apoptosis assessment.

Results: CTS significantly reduced cerebral infarct volume, neurologic deficit scores, pro-inflammatory cytokine production (IL-6, TNF-α, and IL-1β), apoptotic protein expression (cleaved caspase-3) of mice after tMCAO challenge. Furthermore, CTS attenuated CD16+ M1-type and elevated CD206+ M2-type microglia in vivo or in vitro.

Conclusions: We propose that the neuroprotective effect of CTS in the I/R or H/R context are explained modulation of microglial polarization, suggesting therapeutic potential for cerebral ischemic stroke.

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隐丹参酮降低脑缺血再灌注损伤引起的神经毒性，涉及小胶质细胞极化的调节。

背景:二萜隐丹参酮(CTS)具有广泛的生物学功能，包括抑制肿瘤生长、炎症和细胞凋亡。本研究旨在探讨CTS对脑缺血再灌注(I/R)损伤的可能作用及其机制。方法:对雄性C57BL/6J小鼠进行短暂性大脑中动脉闭塞(tMCAO)和小鼠小胶质细胞BV2缺氧/再灌注(H/R)损伤，分别模拟I/R和缺血/缺氧/再灌注(H/R)损伤。在MCAO开始后0.5 h (10 mg/kg)或OGD后2 h (20μM)给予CTS。测量梗死体积和神经功能缺损。采用免疫荧光、qPCR和western blot检测细胞因子、凋亡标志物和M1/M2表型特异性基因的表达。流式细胞术检测M1/M2亚群或Annexin V/PI细胞凋亡。结果:CTS显著降低小鼠脑梗死体积、神经功能缺损评分、促炎细胞因子(IL-6、TNF-α和IL-1β)的产生、凋亡蛋白(cleaved caspase-3)的表达。此外，CTS在体内和体外均能减弱CD16+ m1型和升高CD206+ m2型小胶质细胞。结论:我们认为CTS在I/R或H/R情况下的神经保护作用可以通过调节小胶质细胞极化来解释，提示其对缺血性脑卒中的治疗潜力。

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来源期刊

Restorative neurology and neuroscience 医学-神经科学

CiteScore

5.40

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： This interdisciplinary journal publishes papers relating to the plasticity and response of the nervous system to accidental or experimental injuries and their interventions, transplantation, neurodegenerative disorders and experimental strategies to improve regeneration or functional recovery and rehabilitation. Experimental and clinical research papers adopting fresh conceptual approaches are encouraged. The overriding criteria for publication are novelty, significant experimental or clinical relevance and interest to a multidisciplinary audience. Experiments on un-anesthetized animals should conform with the standards for the use of laboratory animals as established by the Institute of Laboratory Animal Resources, US National Academy of Sciences. Experiments in which paralytic agents are used must be justified. Patient identity should be concealed. All manuscripts are sent out for blind peer review to editorial board members or outside reviewers. Restorative Neurology and Neuroscience is a member of Neuroscience Peer Review Consortium.