Targeting Oxidative Stress and Inflammation to Prevent Ischemia-Reperfusion Injury

Abstract

The cerebral ischemia injury can result in neuronal death and/or functional impairment, which leads to further damage and dysfunction after recovery of blood supply. Cerebral ischemia/reperfusion injury (CIRI) often causes irreversible brain damage and neuronal injury and death, which involves many complex pathological processes including oxidative stress, amino acid toxicity, the release of endogenous substances, inflammation and apoptosis. Oxidative stress and inflammation are interactive and play critical roles in ischemia/reperfusion injury in the brain. Oxidative stress is important in the pathological process of ischemic stroke and is critical for the cascade development of ischemic injury. Oxidative stress is caused by reactive oxygen species (ROS) during cerebral ischemia and is more likely to lead to cell death and ultimately brain death after reperfusion. During reperfusion especially, superoxide anion free radicals, hydroxyl free radicals, and nitric oxide (NO) are produced, which can cause lipid peroxidation, inflammation and cell apoptosis. Inflammation alters the balance between pro-inflammatory and anti-inflammatory factors in cerebral ischemic injury. Inflammatory factors can therefore stimulate or exacerbate inflammation and aggravate ischemic injury. Neuroprotective therapies for various stages of the cerebral ischemia cascade response have received widespread attention. At present, neuroprotective drugs mainly include free radical scavengers, anti-inflammatory agents, and anti-apoptotic agents. However, the molecular mechanisms of the interaction between oxidative stress and inflammation, and their interplay with different types of programmed cell death in ischemia/reperfusion injury are unclear. The development of a suitable method for combination therapy has become a hot topic.

Anti-inflammatory Efficacy of Berberine Nanomicelle for Improvement of Cerebral Ischemia: Formulation, Characterization and Evaluation in Bilateral Common Carotid Artery Occlusion Rat Model

“…BCCAO model was used to induce stroke into rat's brain. An increase in in ammation cytokines and MDA have been reported after induce stroke [34]. In the present study, the results of treated groups (BBR and BBR-loaded micelle) showed signi cantly decreased in TNF-α, IL-1ß, MDA levels in comparison with the stroke group.…”

Neuroprotective Potentials of Marine Algae and Their Bioactive Metabolites: Pharmacological Insights and Therapeutic Advances

“…If the patient survives, the affected brain areas accompany the secondary damage due to the restoration of blood flow and reoxygenation. This ischemia/reperfusion (I/R) event initiates mitochondrial ROS generation [ 58 ] and subsequent inflammatory response [ 59 ].…”

FABP4 alleviates endoplasmic reticulum stress‑mediated ischemia‑reperfusion injury in PC12 cells via regulation of PPARγ

“…During 8 h of OGD, cell viability was gradually downregulated and FABP4 was gradually increased, suggesting that FABP4 had a harmful effect on PC12 cells under OGD/R conditions, which was consistent with the results reported in myocardial IR injury ( 23 ). Oxidative stress and inflammation serve as the main pathogenesis of I/R injury, and effective prevention of oxidative stress and inflammation is conducive to ameliorate I/R injury ( 24 ). In the present study, FABP4-silencing decreased the expression of inflammatory factors, IL-1β, IL-6 and TNF-α, and the decrease in ROS and increase in SOD demonstrated that FABP4 siRNA relieved oxidative stress.…”