• Heena Khan, Amarjot Kaur Grewal, Manish Kumar, and Thakur Gurjeet Singh.
• Chitkara College of Pharmacy, Chitkara University, Punjab, India. Electronic address: Heena@chitkara.edu.in.
• Neuroscience. 2022 May 21; 491: 23-31.

AbstractIschemia-reperfusion (I/R) injury often follows cardiovascular aberrations that predispose the patient to be neurological and cognitive abnormalities. Pharmacological postconditioning (pPoCo) aims to mitigate I/R origin cerebral infarction and neurobehavioral impairment. Protocatechuic acid (PCA) is a natural polyphenol possessing anti-oxidant and anti-inflammatory activities. This study investigated the effects of PCA pPoCo using a global I/R mice prototype. Mice were injected PCA (50 and 100 mg/kg) immediately after bilateral common carotid artery occlusion (17 min) followed by 24 h reperfusion. Trigonelline (10 mg/kg) was administered separately before I/R surgery to assess the role of the Nrf2 pathway in PCA and I/R treated mice. Results displayed neurological deficits 24 h post-reperfusion, and I/R triggered sensorimotor and memory deficits that were attenuated by PCA. PCA pPoCo increased antioxidants and Nrf2 expression in the brain against I/R injury. In I/R mice, PCA pPoCo attenuated lipid peroxidation, inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6), and myeloperoxidase activity. Histopathology revealed a decrease in total infarct area (TTC staining) and cortical neuron density by I/R surgery that was attenuated by PCA. Trigonelline antagonized beneficial effects of PCA pPoCo and attenuated Nrf2 pathway in I/R mice model. PCA pPoCo dose-dependently improves neurobehavioral functions against global I/R injury via the Nrf2 mechanism.Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.

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