Limb remote ischemic conditioning increases Notch signaling activity and promotes arteriogenesis in the ischemic rat brain

Publication date: 15 March 2018
Source:Behavioural Brain Research, Volume 340
Author(s): Changhong Ren, Sijie Li, Brian Wang, Rongrong Han, Ning Li, Jinhuan Gao, Xiaohua Li, Kunlin Jin, Xunming Ji
Background and purposeWe tested the hypothesis that limb remote ischemic conditioning (LRIC) treatment promotes arteriogenesis and increases Notch signaling activity during stroke recovery.MethodsAdult 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.ResultsLRIC 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.ConclusionThese 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.



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