Remote Limb Ischemic Preconditioning: A Neuroprotective Technique in Rodents

Abstract

Sublethal ischemia protects tissues against subsequent, more severe ischemia through the upregulation of endogenous mechanisms in the affected tissue. Sublethal ischemia has also been shown to upregulate protective mechanisms in remote tissues. A brief period of ischemia (5-10 min) in the hind limb of mammals induces self-protective responses in the brain, lung, heart and retina. The effect is known as remote ischemic preconditioning (RIP). It is a therapeutically promising way of protecting vital organs, and is already under clinical trials for heart and brain injuries. This publication demonstrates a controlled, minimally invasive method of making a limb -specifically the hind limb of a rat -ischemic. A blood pressure cuff developed for use in human neonates is connected to a manual sphygmomanometer and used to apply 160 mmHg pressure around the upper part of the hind limb. A probe designed to detect skin temperature is used to verify the ischemia, by recording the drop in skin temperature caused by pressure-induced occlusion of the leg arteries, and the rise in temperature which follows release of the cuff. This method of RIP affords protection to the rat retina against bright light-induced damage and degeneration. Video LinkThe video component of this article can be found at

Neuroprotection by remote ischemic conditioning in the setting of acute ischemic stroke: a preclinical two-centre study

“…RIC was performed as 4 cycles of 5-min left hind limb ischemia 30 interleaved with 5-min reperfusion, using an inflatable 12-mm cuff (IVM, USA), which was inflated to 200 mmHg and subsequently deflated. The efficiency of blood cessation with hind limb cuff inflation in rats had previously been confirmed 31 . Of note, because of its mechanical nature, the allocation of rat to treatment group could not be concealed from the investigator performing the RIC treatment (M.B.…”

Glucagon-like peptide-1 (GLP-1) receptor activation dilates cerebral arterioles, increases cerebral blood flow, and mediates remote (pre)conditioning neuroprotection against ischaemic stroke

“…The animals were randomized into four experimental groups: (1) rats with MCAO/sham-RIC; (2) rats subjected to RIC starting 10 min before the onset of reperfusion; RIC protocol involved 4 cycles of 5 min left hind limb ischaemia interleaved with 5-min reperfusion periods [ 10 , 29 ], applied using an inflatable 12-mm cuff (IVM, USA). The cuff was inflated to 200 mmHg to stop the blood flow through the limb, as reported previously [ 12 ]; (3) rats with MCAO treated with a competitive GLP-1R antagonist Exendin (9–39) (Ex9, 50 μg kg −1 , intravenously) 20 min before the onset of reperfusion; (4) rats subjected to the RIC protocol starting 10 min before the onset of reperfusion and treated with Ex9 10 min prior to the first episode of RIC. Experimental timeline is illustrated by Fig.…”

Efficacy of remote limb ischemic conditioning on poststroke cognitive impairment

“…In principle, RIC applies transient ischemic stimulation to one organ to induce an endogenous protective response against severe ischemic injury in another distant organ. For example, remote limb ischemic conditioning (RLIC) applies intermittent interruptions of blood supply to non-vital body organs (the limb) to protect vital organs (the heart or brain) from ischemic injury (Brandli, 2015;Pan et al, 2016).…”