Neurobehavioral and Imaging Correlates of Hippocampal Atrophy in a Mouse Model of Vascular Cognitive Impairment

Kristen L. Zuloaga, Wenri Zhang, Lauren A. Yeiser, Blair Stewart, Ayaka Kukino, Xiao Nie, Natalie E. Roese, Marjorie R. Grafe, Martin M. Pike, Jacob Raber, Nabil J. Alkayed

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Vascular cognitive impairment (VCI) is the second most common cause of dementia. Reduced cerebral blood flow is thought to play a major role in the etiology of VCI. Therefore, chronic cerebral hypoperfusion has been used to model VCI in rodents. The goal of the current study was to determine the histopathological and neuroimaging substrates of neurocognitive impairments in a mouse model of chronic cerebral hypoperfusion induced by unilateral common carotid artery occlusion (UCCAO). Mice were subjected to sham or right UCCAO (VCI) surgeries. Three months later, neurocognitive function was evaluated using the novel object recognition task, Morris water maze, and contextual and cued fear-conditioning tests. Next, cerebral perfusion was evaluated with dynamic susceptibility contrast magnetic resonance imaging (MRI) using an ultra-high field (11.75 T) animal MRI system. Finally, brain pathology was evaluated using histology and T2-weighted MRI. VCI, but not sham, mice had significantly reduced cerebral blood flow in the right vs. left cerebral cortex. VCI mice showed deficits in object recognition. T2-weighted MRI of VCI brains revealed enlargement of lateral ventricles, which corresponded to areas of hippocampal atrophy upon histological analysis. In conclusion, our data demonstrate that the UCCAO model of chronic hypoperfusion induces hippocampal atrophy and ventricular enlargement, resulting in neurocognitive deficits characteristic of VCI.

Original languageEnglish (US)
Pages (from-to)390-398
Number of pages9
JournalTranslational Stroke Research
Volume6
Issue number5
DOIs
StatePublished - Oct 10 2015

Keywords

  • Cerebral blood flow
  • Chronic cerebral hypoperfusion
  • Cognitive impairment
  • Vascular dementia

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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