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Limb Ischemic Conditioning Improved Cognitive Deficits via eNOS-Dependent Augmentation of Angiogenesis after Chronic

Changhong Ren1,2,3,4, Ning Li1,5, Sijie Li1,4

  • 11Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.

Aging and Disease
|October 2, 2018
PubMed

Insights

Limb remote ischemic conditioning (LRIC) improved cerebral perfusion and cognitive function in a rat model of chronic cerebral hypoperfusion. LRIC promoted angiogenesis and increased phosphorylated endothelial nitric oxide synthase (p-eNOS) activity, suggesting a therapeutic potential for vascular dementia.

Area of Science:

  • Neuroscience
  • Cardiovascular Science
  • Regenerative Medicine

Background:

  • Chronic cerebral hypoperfusion (CCH) from arterial stenosis contributes to vascular dementia and Alzheimer's disease.
  • Previous research indicated Limb Remote Ischemic Conditioning (LRIC) enhances cerebral perfusion in patients with intracranial arterial stenosis.

Purpose of the Study:

  • To investigate if LRIC promotes angiogenesis and increases phosphorylated endothelial nitric oxide synthase (p-eNOS) activity in a rat model of CCH.
  • To evaluate the therapeutic effects of LRIC on cognitive impairment and hippocampal cell survival in CCH rats.

Main Methods:

  • Adult male Sprague-Dawley rats were subjected to bilateral carotid artery occlusion (2VO) with or without LRIC treatment.
  • Cerebral blood flow (CBF) was measured using laser speckle contrast imaging.
  • Cognitive function was assessed via spatial learning and memory tests.
  • Immunohistochemistry and Western blot analysis were used to evaluate angiogenesis, cell death, and p-eNOS expression in the hippocampus.

Main Results:

  • LRIC treatment significantly increased cerebral perfusion and improved spatial learning and memory deficits in 2VO rats.
  • LRIC prevented neuronal cell death in the CA1 region and promoted angiogenesis in the hippocampus.
  • LRIC therapy elevated p-eNOS expression in the hippocampus.
  • Inhibition of eNOS (endothelial nitric oxide synthase) diminished the beneficial effects of LRIC on angiogenesis and cognitive function.

Conclusions:

  • LRIC effectively improves cerebral perfusion and cognitive function in a rat model of CCH.
  • The pro-angiogenic effects of LRIC in the hippocampus are, in part, mediated by the eNOS/NO pathway.
  • LRIC shows potential as a therapeutic strategy for conditions associated with CCH and cognitive impairment.

Keywords:
NOangiogenesischronic cerebral hypoperfusioneNOSlimb ischemic conditioning

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