Quercetin attenuated ischemic stroke induced neurodegeneration by modulating glutamatergic and synaptic signaling pathways
Fawad Ali Shah,
Faisal Albaqami,
Abdullah Alattar,
Reem Alshaman,
Sawsan A. Zaitone,
Attia M. Gabr,
Abdel-Moneim Hafez Abdel-Moneim,
Mohamed El dosoky,
Phil Ok Koh
Affiliations
Fawad Ali Shah
Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia; Corresponding author.
Faisal Albaqami
Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia
Abdullah Alattar
Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia
Reem Alshaman
Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia
Sawsan A. Zaitone
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt
Attia M. Gabr
Pharmacology and Therapeutics Department, College of Medicine, Qassim University, Qassim, Saudi Arabia; Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, 41522, Egypt
Abdel-Moneim Hafez Abdel-Moneim
Department of Physiology, College of Medicine, Qassim University, Qassim, Saudi Arabia; Department of Physiology, Faculty of Medicine, Mansoura University, Egypt
Mohamed El dosoky
Department of Neuroscience Technology, College of Applied Medical Sciences in Jubail, Imam Abdulrahman Bin Faisal University, Jubail, Saudi Arabia
Phil Ok Koh
Department of Anatomy and Histology, College of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, 501 Jinjudaero, Jinju, 52828, South Korea
Ischemic strokes originate whenever the circulation to the brain is interrupted, either temporarily or permanently, resulting in a lack of oxygen and other nutrients. This deprivation primarily impacts the cerebral cortex and striatum, resulting in neurodegeneration. Several experimental stroke models have demonstrated that the potent antioxidant quercetin offers protection against stroke-related damage. Multiple pathways have been associated with quercetin's ability to safeguard the brain from ischemic injury. This study examines whether the administration of quercetin alters glutamate NMDA and GluR1 receptor signaling in the cortex and striatum 72 h after transient middle cerebral artery occlusion. The administration of 10 mg/kg of quercetin shielded cortical and striatal neurons from cell death induced by ischemia in adult SD rats. Quercetin reversed the ischemia-induced reduction of NR2a/PSD95, consequently promoting the pro-survival AKT pathway and reducing CRMP2 phosphorylation. Additionally, quercetin decreased the levels of reactive oxygen species and inflammatory pathways while increasing the expression of the postsynaptic protein PSD95. Our results suggest that quercetin may be a promising neuroprotective drug for ischemic stroke therapy as it recovers neuronal damage via multiple pathways.
