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

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

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.

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Abbreviations

rCCAO:

Right common carotid artery occlusion

2VO:

Bilateral occlusion of common carotid artery

RAWM:

Radial arm water maze

MWM:

Morris water maze

ITI:

Inter-trial time interval

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Acknowledgments

We thank Ratana Ninturk and Chatsumal Pholseang for their valuable technical assistance. This study was supported by Siriraj Thesis Scholarship, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand.

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Author notes

  1. Mayuree H. Tantisira

    Present address: Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, 20131, Thailand

Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Road, Bangkoknoi, Bangkok, 10700, Thailand

    Kanokwan Tilokskulchai

  2. Department of Biology, Faculty of Science, Kasetsart University, Bang Khen, Bangkok, 10900, Thailand

    Khwanjai Thong-asa

  3. Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand

    Supin Chompoopong

  4. Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand

    Mayuree H. Tantisira

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  1. Khwanjai Thong-asa
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  3. Mayuree H. Tantisira
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Correspondence to Kanokwan Tilokskulchai.

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Thong-asa, K., Chompoopong, S., Tantisira, M.H. et al. Reversible short-term and delayed long-term cognitive impairment induced by chronic mild cerebral hypoperfusion in rats. J Neural Transm 120, 1225–1235 (2013). https://doi.org/10.1007/s00702-012-0937-1

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  • DOI: https://doi.org/10.1007/s00702-012-0937-1

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