Remote ischemic preconditioning effects on brain vasculature

Remote ischemic preconditioning (RIPC), a brief transient episode of ischemia/reperfusion in distant tissues or organs, renders remote tissues and organs resistant to a subsequent prolonged ischemic insult.¹ The RIPC stimulus may include occlusion of blood vessels in animal models, reduction of respired atmospheric oxygen intermittently before ischemia, or occlusion of the arteries of the arm by tourniquet.² First described in a dog model of cardiac reperfusion in the 1980s, exposure to preclinical ischemic preconditioning involving the temporary occlusion of the coronary arteries restricted the myocardial injury caused by a subsequent sustained occlusion.³ Clinical outcomes in a number of ischemic conditions in humans have shown consistent improvement with RIPC, including decreased infarct size after myocardial infarction,^4,5 slower progression of imaging lesions and cognitive decline in patients with cerebral small vessel disease,⁶ accelerated recovery from hypoxic ischemic brain injury after cardiac arrest,⁷ and reduced subsequent infarct volumes in patients with severe carotid stenosis undergoing carotid artery stenting.⁸ RIPC protects cells and tissue from future ischemia via a complex interplay of inflammatory, apoptotic, and neuroregenerative pathways that operate in parallel and in a complex manner.^2,9 In the brain, RIPC primes nitric oxide formation, storage, and signaling and triggers synthesis of proapoptotic and antiapoptotic proteins such as B-cell lymphoma 2.² It also stimulates neurogenesis and angiogenesis by upregulating brain-derived neurotropic factor and vascular endothelial growth factor production.²