Spatial Memory Disturbance Following Transient Brain Ischemia is Associated with Vascular Remodeling in Hippocampus

Kobe J Med Sci. 2018 Oct 15;64(3):E93-E106.


A number of studies have investigated the effects of ischemic injury on functional and cellular characteristics of hippocampus. There is only a limited study on vascular remodeling of it. The present study aimed at examining vascular remodeling in hippocampus and spatial memory disturbances after transient brain ischemia. Male Wistar rats were randomly divided into four groups, i.e. sham operated (SHAM), transient brain ischemia with 1 day reperfusion (IR1), 3 day reperfusion (IR3), and 10 days reperfusion (IR10) groups. Transient brain ischemia was induced by bilateral common carotid artery occlusion (BCCAO). The spatial memory test was performed using the Morris water maze (MWM) in SHAM and IR10 groups. The rats were euthanized at day 1, 3 or 10 after BCCAO depending on the groups. The mRNA expressions of SOD2, Bcl-2, NeuN, eNOS, endothelin-1 (ET-1), CD31, VE-cadherin and vascular remodeling of the hippocampus were examined. There were deteriorations of spatial learning ability in IR10 group. The percentages of SOD2 and Bcl-2, the expression of NeuN, decreased and the vascular remodeling was observed in the ischemic groups. The eNOS and CD31 expressions were less in IR10, the VE-cadherin expression was less in all ischemic groups than in SHAM group, while ET-1 expression in IR1 group was higher than any other groups. The spatial memory deterioration after BCCAO is associated with vascular remodeling in hippocampus, characterized by lumen narrowing and smooth muscle thickening of microvessels.

Keywords: bilateral common carotid artery occlusion; hippocampus; ischemic reperfusion injury; spatial memory; vascular remodeling.

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, Nuclear / genetics
  • Cadherins / genetics
  • Disease Models, Animal
  • Endothelin-1 / genetics
  • Gene Expression
  • Genes, bcl-2
  • Hippocampus / blood supply*
  • Hippocampus / physiology
  • Hippocampus / physiopathology*
  • Ischemic Attack, Transient / complications
  • Ischemic Attack, Transient / pathology
  • Ischemic Attack, Transient / psychology*
  • Male
  • Maze Learning / physiology
  • Memory Disorders / etiology*
  • Memory Disorders / pathology
  • Memory Disorders / physiopathology
  • Nerve Tissue Proteins / genetics
  • Nitric Oxide Synthase Type III / genetics
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Spatial Memory / physiology
  • Superoxide Dismutase / genetics
  • Vascular Remodeling / genetics
  • Vascular Remodeling / physiology*


  • Antigens, CD
  • Antigens, Nuclear
  • Cadherins
  • Endothelin-1
  • Nerve Tissue Proteins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • RNA, Messenger
  • Rbfox3 protein, rat
  • cadherin 5
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Superoxide Dismutase
  • superoxide dismutase 2