Neuroprotective effect of 3,3'-diindolylmethane and ɑ-naphthoflavone, aryl hydrocarbon receptor modulators in an experimental model of ischemic stroke.

IF 1.7 2区文学 0 LANGUAGE & LINGUISTICS Linguistic Typology Pub Date : 2022-04-18 DOI:10.2174/1871527321666220418120224

Neha Dhir, Ashish Jain, Amit Raj Sharma, Ajay Prakash, Alka Bhatia, Bikash Medhi

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Abstract

Background: The aryl hydrocarbon receptor (AhR) mediated signaling pathway is being emerged as a current target for neuromodulation. The present study was conducted to characterize the neuroprotective action of AhR modulators, i.e., 3,3'-diindolylmethane (DIM) and ɑ-naphthoflavone (ANF) in an experimental model of stroke using transient middle cerebral artery occlusion (MCAO) in Wistar rats.

Methods: The animals were treated with respective AhR modulators via intraperitoneal (i.p) injection 3 hrs after MCAO for 4 days (at 24 h interval). Following transient MCAO, the brain infarct volume, ND scoring, and various neuro behavioural tests were conducted to confirm the ischemic stroke. Further, oxidative stress parameters, inflammatory cytokines, and apoptotic mRNA expression were assessed. The histopathological changes in the brain of the rats were assessed using H&E staining and the results obtained were correlated with the molecular parameters.

Results: Treatment with AhR modulators had significantly decreased the brain infarct volume, ND scoring and improved neuro-behivoral deficits in animals following MCAO. A significant decrease was also observed in the oxidative stress, pro-inflammatory cytokines, and apoptotic mRNA expression in the AhR ligand treated groups. Moreover, a significant improvement was observed in the neuronal damage following MCAO in the treatment groups.

Conclusion: AhR pathway modulation may be taken as a valuable therapeutic target for treating acute ischemic stroke (AIS).

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3,3'-二吲哚甲烷和ɑ-萘黄酮（芳香烃受体调节剂）在缺血性中风实验模型中的神经保护作用

背景：芳基烃受体（AhR）介导的信号通路正在成为神经调节的靶点。本研究采用一过性大脑中动脉闭塞（MCAO）对 Wistar 大鼠进行脑卒中实验模型研究，旨在鉴定 AhR 调节剂（即 3,3'-diindolylmethane (DIM) 和 ɑ-naphthoflavone (ANF)）的神经保护作用：方法：在 MCAO 发生 3 小时后，通过腹腔注射（i.p）相应的 AhR 调节剂对动物进行为期 4 天（间隔 24 小时）的治疗。一过性 MCAO 后，进行脑梗死体积、ND 评分和各种神经行为测试以确认缺血性中风。此外，还对氧化应激参数、炎症细胞因子和细胞凋亡 mRNA 表达进行了评估。使用 H&E 染色法评估大鼠大脑组织病理学变化，并将评估结果与分子参数进行关联：结果：AhR调节剂能显著减少MCAO后动物的脑梗塞体积和ND评分，并改善神经-精神障碍。AhR 配体治疗组的氧化应激、促炎细胞因子和细胞凋亡 mRNA 表达也明显减少。此外，还观察到治疗组在 MCAO 后神经元损伤方面有明显改善：结论：AhR通路调节可作为治疗急性缺血性中风（AIS）的重要治疗靶点。

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来源期刊

Linguistic Typology Multiple-

CiteScore

3.70

自引率

5.00%

发文量

期刊介绍： Linguistic Typology provides a forum for all work of relevance to the study of language typology and cross-linguistic variation. It welcomes work taking a typological perspective on all domains of the structure of spoken and signed languages, including historical change, language processing, and sociolinguistics. Diverse descriptive and theoretical frameworks are welcomed so long as they have a clear bearing on the study of cross-linguistic variation. We welcome cross-disciplinary approaches to the study of linguistic diversity, as well as work dealing with just one or a few languages, as long as it is typologically informed and typologically and theoretically relevant, and contains new empirical evidence.

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