ORCID Identifiers
Document Type
Article
Source of Publication
Biomolecules
Publication Date
5-26-2020
Abstract
Ischemic stroke is categorized by either permanent or transient blood flow obstruction, impeding the distribution of oxygen and essential nutrients to the brain. In this study, we examined the neuroprotective effects of compound A3, a synthetic polyphenolic drug product, against ischemic brain injury by employing an animal model of permanent middle cerebral artery occlusion (p-MCAO). Ischemic stroke induced significant elevation in the levels of reactive oxygen species and, ultimately, provoked inflammatory cascade. Here, we demonstrated that A3 upregulated the endogenous antioxidant enzymes, such as glutathione s-transferase (GST), glutathione (GSH), and reversed the ischemic-stroke-induced nitric oxide (NO) and lipid peroxidation (LPO) elevation in the peri-infarct cortical and striatal tissue, through the activation of endogenous antioxidant nuclear factor E2-related factor or nuclear factor erythroid 2 (Nrf2). In addition, A3 attenuated neuroinflammatory markers such as ionized calcium-binding adapter molecule-1 (Iba-1), cyclooxygenase-2 (COX-2), tumor necrotic factor-α (TNF-α), toll-like receptors (TLR4), and nuclear factor-κB (NF-κB) by down-regulating p-JNK as evidenced by immunohistochemical results. Moreover, treatment with A3 reduced the infarction area and neurobehavioral deficits. We employed ATRA to antagonize Nrf2, which abrogated the neuroprotective effects of A3 to further assess the possible involvement of the Nrf2 pathway, as demonstrated by increased infarction and hyperexpression of inflammatory markers. Together, our findings suggested that A3 could activate Nrf2, which in turn regulates the downstream antioxidants, eventually mitigating MCAO-induced neuroinflammation and neurodegeneration.
DOI Link
ISSN
Publisher
MDPI AG
Volume
10
Issue
6
First Page
816
Disciplines
Chemistry | Life Sciences
Keywords
A3, all-trans retinoic acid, antioxidant system, middle cerebral artery occlusion, neurodegeneration
Scopus ID
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Mohsin Alvi, Arooj; Al Kury, Lina Tariq; Umar Ijaz, Muhammad; Ali Shah, Fawad; Tariq Khan, Muhammad; Sadiq Sheikh, Ahmed; Nadeem, Humaira; Khan, Arif Ullah; Zeb, Alam; and Li, Shupeng, "Post-Treatment of Synthetic Polyphenolic 1,3,4 Oxadiazole Compound A3, Attenuated Ischemic Stroke-Induced Neuroinflammation and Neurodegeneration" (2020). All Works. 2740.
https://zuscholars.zu.ac.ae/works/2740
Indexed in Scopus
yes
Open Access
yes
Open Access Type
Gold: This publication is openly available in an open access journal/series