Some new prospects in the understanding of the molecular basis of the pathogenesis of stroke.
Stroke is one of the leading causes of mortality and morbidity in advanced countries of the world. Despite the fact that reactive oxygen and nitrogen species (ROS and RNS) are the by-products of normal metabolic processes and mediate important physiological processes, they can inflict damage to the cell if produced in excess due to oxidative stress. In the present review, we focus on the cellular and molecular aspects of ROS and RNS generation and its role in the pathogenesis of stroke produced by hypoxia-reperfusion (H-R) phenomena that elicit oxidative stress. We outline the reasons for the vulnerability of the brain to ischaemic insult, chronic infection and inflammation as well as the natural defence mechanisms against radical mediated injury. We deal with the effect of ROS and RNS on intracellular signaling pathways together with the phenomena of apoptosis, mitochondrial injury and survival associated with these pathways. The intracellular signaling mechanisms influenced by reactive species can have significant effects on the outcome of the condition. Future studies should focus on understanding the molecular mechanisms involved in the action of anti-radicals agents, and their mode of action.
Saeed
Sheikh Arshad
SA
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. arshad.saeed@iccs.edu
Shad
Kaneez Fatima
KF
Saleem
Taimur
T
Javed
Faisal
F
Khan
Muhammad Umair
MU
D000818:Animals; D001921:Brain / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007239:Infections / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D026361:Reactive Nitrogen Species / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D020521:Stroke / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
D005609:Free Radicals; D016877:Oxidants; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species