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Updated: Mar 13, 2026
Remote Limb Ischemic Preconditioning: A Neuroprotective Technique in Rodents
Published on: June 2, 2015
Limb remote ischemic conditioning increases Notch signaling activity and promotes arteriogenesis in the ischemic rat
Changhong Ren1, Sijie Li2, Brian Wang3
1Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Center for Neuroscience Discovery, Institute for Healthy Aging, University of North Texas Health Science Center at Fort Worth, TX 76107, USA; Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing 100053, China; Center for Stroke, Beijing Institute for Brain Disorder, Beijing 100069, China.
Background And Purpose:
We tested the hypothesis that limb remote ischemic conditioning (LRIC) treatment promotes arteriogenesis and increases Notch signaling activity during stroke recovery.
Methods:
Adult male Sprague Dawley rats were subjected to middle cerebral artery occlusion (MCAO). LRIC was applied after the onset of focal ischemia (per-conditioning), followed by repeated short episodes of remote ischemia 24h after reperfusion (post-conditioning). Cerebral blood flow (CBF) was measured by Laser Doppler Flowmetry. Immunohistochemistry was used to reveal α-smooth muscle actin (α-SMA) immunopositive cells in the arteries of the brain. The cerebral angioarchitecture was visualized with a latex perfusion technique.
Results:
LRIC treatment significantly elevated local cerebral blood flow and increased arteriogenesis as indicated by increased arterial diameter and vascular smooth muscle cell proliferation in the ischemic brain. The increased arteriogenesis significantly correlated with the functional outcome after stroke. Furthermore, LRIC treatment upregulated the expressions of Notch1 and Notch intracellular domain (NICD) in arteries surrounding the ischemic area.
Conclusion:
These results suggest that the therapeutic effects of LRIC may involve the promotion of arteriogenesis during the recovery phase after focal cerebral ischemia and that Notch1 signaling seems to be an important player in limb remote ischemia-mediated arteriogenesis.
