Journal of Neural Transmission

, Volume 120, Issue 8, pp 1225–1235

Reversible short-term and delayed long-term cognitive impairment induced by chronic mild cerebral hypoperfusion in rats

  • Khwanjai Thong-asa
  • Supin Chompoopong
  • Mayuree H. Tantisira
  • Kanokwan Tilokskulchai
Neurology and Preclinical Neurological Studies - Original Article

DOI: 10.1007/s00702-012-0937-1

Cite this article as:
Thong-asa, K., Chompoopong, S., Tantisira, M.H. et al. J Neural Transm (2013) 120: 1225. doi:10.1007/s00702-012-0937-1


Chronic cerebral hypoperfusion induced by aging in combination with vascular disorder potentially contributes to the development of vascular dementia. This study aimed to investigate the age-related changes in spatial performances in chronic mild cerebral hypoperfusion induced by permanent right common carotid artery occlusion (rCCAO) in rats. Four-month-old male Sprague–Dawley rats (n = 20) were randomly assigned into sham and rCCAO groups. Spatial performances of young adult rats (age 4–8 months) were evaluated repeatedly by the radial arm water maze at 6 days, and 1, 2 and 4 months after surgery. The spatial performance was re-assessed by the Morris water maze when the rats were 18 months old. The present results revealed that the rCCAO rats developed progressive deficit in spatial learning and memory, starting from day 6 and significant deficit was found at 2 months after rCCAO (p < 0.05). However, the spatial performance of the rCCAO rats was recovered at 4 months after surgery. Testing of the cognitive flexibility of the aged rCCAO rats (18 months old), indicated that the learning flexibility of the aged rCCAO rats was significantly impaired. This deficit was found in parallel with pronounced white matter damage in the corpus callosum and internal capsule and significant cell death in the dorsal hippocampus. Our results suggested that vascular risk insult in young adult rats resulted in spatial learning deficit which could be completely compensated later on. However, such previous vascular risk could be exacerbated by advancing age and subsequently lead to a deficit in cognitive flexibility with white matter damage and significant neuronal death in the dorsal hippocampus.


Chronic cerebral hypoperfusion Unilateral common carotid artery occlusion Spatial learning and memory Aging Cognitive flexibility 



Right common carotid artery occlusion


Bilateral occlusion of common carotid artery


Radial arm water maze


Morris water maze


Inter-trial time interval

Copyright information

© Springer-Verlag Wien 2012

Authors and Affiliations

  • Khwanjai Thong-asa
    • 2
  • Supin Chompoopong
    • 3
  • Mayuree H. Tantisira
    • 4
    • 5
  • Kanokwan Tilokskulchai
    • 1
  1. 1.Department of Physiology, Faculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand
  2. 2.Department of Biology, Faculty of ScienceKasetsart UniversityBangkokThailand
  3. 3.Department of Anatomy, Faculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand
  4. 4.Faculty of Pharmaceutical SciencesChulalongkorn UniversityBangkokThailand
  5. 5.Faculty of Pharmaceutical SciencesBurapha UniversityChonburiThailand