Limb ischemic conditioning improved cognitive deficits via eNOS-dependent augmentation of angiogenesis after chronic cerebral hypoperfusion in rats

Changhong Ren, Ning Li, Sijie Li, Rongrong Han, Qingjian Huang, Jiangnan Hu, Kunlin Jin, Xunming Ji

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Intracranial and extracranial arterial stenosis, the primary cause of chronic cerebral hypoperfusion (CCH), is a critical reason for the pathogenesis of vascular dementia and Alzheimer's disease characterized by cognitive impairments. Our previous study demonstrated that limb remote ischemic conditioning (LRIC) improved cerebral perfusion in intracranial arterial stenosis patients. The current study aimed to test whether LRIC promotes angiogenesis and increases phosphorylated endothelial nitric oxide synthase (p-eNOS) activity in CCH rat model. Adult male Sprague-Dawley rats were randomly assigned to three different groups: sham group, bilateral carotid artery occlusion (2VO) group and 2VO+LRIC group. Cerebral Blood Flow (CBF) was measured with laser speckle contrast imager at 4 weeks. Cognitive testing was performed at four and six weeks after 2VO surgery. We demonstrated that LRIC treatment increased cerebral perfusion and improved the CCH induced spatial learning and memory impairment. Immunohistochemistry confirmed that LRIC prevented cell death in the CA1 region, and increased the number of vessels and angiogenesis in the hippocampus after 2VO. Western blot analysis shows that LRIC therapy significantly increased p-eNOS expression in the hippocampus when compared with 2VO rats. Moreover, eNOS inhibitor reduced the effect of LRIC on angiogenesis in the hippocampus and spatial learning and memory function. Our data suggested that LRIC promoted angiogenesis, which is mediated, in part, by eNOS/NO.

Original languageEnglish
Pages (from-to)869-879
Number of pages11
JournalAging and Disease
Volume9
Issue number5
DOIs
StatePublished - 1 Jan 2018

Fingerprint

Extremities
Hippocampus
Nitric Oxide Synthase Type III
Cerebrovascular Circulation
Pathologic Constriction
Perfusion
Vascular Dementia
Conditioning (Psychology)
Behavior Therapy
Vascular Diseases
Carotid Arteries
Sprague Dawley Rats
Alzheimer Disease
Lasers
Cell Death
Western Blotting
Immunohistochemistry

Keywords

  • Angiogenesis
  • Chronic cerebral hypoperfusion
  • ENOS
  • Limb ischemic conditioning
  • NO

Cite this

Ren, Changhong ; Li, Ning ; Li, Sijie ; Han, Rongrong ; Huang, Qingjian ; Hu, Jiangnan ; Jin, Kunlin ; Ji, Xunming. / Limb ischemic conditioning improved cognitive deficits via eNOS-dependent augmentation of angiogenesis after chronic cerebral hypoperfusion in rats. In: Aging and Disease. 2018 ; Vol. 9, No. 5. pp. 869-879.
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Limb ischemic conditioning improved cognitive deficits via eNOS-dependent augmentation of angiogenesis after chronic cerebral hypoperfusion in rats. / Ren, Changhong; Li, Ning; Li, Sijie; Han, Rongrong; Huang, Qingjian; Hu, Jiangnan; Jin, Kunlin; Ji, Xunming.

In: Aging and Disease, Vol. 9, No. 5, 01.01.2018, p. 869-879.

Research output: Contribution to journalArticle

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