title: Limb remote ischemic conditioning increases Notch signaling activity and promotes arteriogenesis in the ischemic rat brain.
abstract: We tested the hypothesis that limb remote ischemic conditioning (LRIC) treatment promotes arteriogenesis and increases Notch signaling activity during stroke recovery.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Institute 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.
authors: Changhong
authors: C
authors: Ren
authors: Emergency Department, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing 100053, China.
authors: Sijie
authors: S
authors: Li
authors: Center for Neuroscience Discovery, Institute for Healthy Aging, University of North Texas Health Science Center at Fort Worth, TX 76107, USA.
authors: Brian
authors: B
authors: Wang
authors: Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing 100053, China; Center for Stroke, Beijing Institute for Brain Disorder, Beijing 100069, China.
authors: Rongrong
authors: R
authors: Han
authors: Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing 100053, China; Center for Stroke, Beijing Institute for Brain Disorder, Beijing 100069, China.
authors: Ning
authors: N
authors: Li
authors: Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors: Jinhuan
authors: J
authors: Gao
authors: Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing 100053, China; Center for Stroke, Beijing Institute for Brain Disorder, Beijing 100069, China.
authors: Xiaohua
authors: X
authors: Li
authors: Institute 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.
authors: Kunlin
authors: K
authors: Jin
authors: Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing 100053, China. Electronic address: jixm@ccmu.edu.cn.
authors: Xunming
authors: X
authors: Ji
mesh_terms: D000818:Animals; D001158:Arteries / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D006614:Hindlimb / Q000098:blood supply*; D057775:Ischemic Postconditioning / Q000379:methods; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000378:metabolism*; D012039:Regional Blood Flow / Q000502:physiology; D015398:Signal Transduction; D020521:Stroke / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: C497763:Notch1 protein, rat; D051881:Receptor, Notch1
keywords: Arteriogenesis; Ischemic stroke; Limb remote ischemic conditioning; Notch1 signaling