Redox Signaling Pathways Involved in Neuronal Ischemic Preconditioning

Abstract

There is extensive evidence that the restoration of blood flow following cerebral ischemia contributes greatly to the pathophysiology of ischemia mediated brain injury. The initiating stimulus of reperfusion injury is believed to be the excessive production of reactive oxygen (ROS) and nitrogen (RNS) species by the mitochondria. ROS and RNS generation leads to mitochondrial protein, lipid and DNA oxidation which impedes normal mitochondrial physiology and initiates cellular death pathways. However not all ROS and RNS production is detrimental. It has been demonstrated that low levels of ROS production are protective and may serve as a trigger for activation of ischemic preconditioning. Ischemic preconditioning is a neuroprotective mechanism which is activated upon a brief sublethal ischemic exposure and is sufficient to provide protection against a subsequent lethal ischemic insult. Numerous proteins and signaling pathways have been implicated in the ischemic preconditioning neuroprotective response. In this review we examine the origin and mechanisms of ROS and RNS production following ischemic/reperfusion and the role of free radicals in modulating proteins associated with ischemic preconditioning neuroprotection.

5d, a novel analogue of 3-n-butylphthalide, protects brains against nervous injury induced by ischemia/reperfusion through Akt/Nrf2/NOX4 signaling pathway

“…Nrf2 is a key transcription factor that regulates antioxidant genes as an adaptive response to oxidative stress or pharmacological stimuli. 30 To investigate the effect of 5d on the Nrf2 signaling, the cellular locations of Nrf2 and kelch-like ECHassociated protein 1 (Keap-1) were evaluated aer I/R. Immunoblot analysis revealed that the expression of Nrf2 in the nuclear fraction was signicantly higher in 5d-treated groups than in the Model group.…”

Potential preventative impact of aloe-emodin nanoparticles on cerebral stroke-associated myocardial injury by targeting myeloperoxidase: In supporting with In silico and In vivo studies

“…Excessive ROS production during cerebral I/R injury causes cellular and molecular oxidative injury, exacerbating both cardiac and cerebral tissue damage [ 1 ]. ROS play a pivotal role in coordinating several deleterious processes that contribute to lipid peroxidation, DNA fragmentation and protein oxidation and preferentially damage highly oxygenated cells [ 2 , 3 ]. Oxidative events observed in myocardial tissues after stroke have been associated with arrhythmogenesis, depressed contractility and myocardial remodeling, highlighting the profound effect that cerebral events have on cardiac function and vice versa [ 4 , 5 ].…”