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 Grafe, Martin Pike, Jacob Raber, Nabil Alkayed

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 - Jun 5 2015

Fingerprint

Atrophy
Blood Vessels
Common Carotid Artery
Cerebrovascular Circulation
Magnetic Resonance Imaging
Cognitive Dysfunction
Lateral Ventricles
Brain
Neuroimaging
Cerebral Cortex
Fear
Dementia
Rodentia
Histology
Perfusion
Pathology
Water

Keywords

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

ASJC Scopus subject areas

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

Cite this

Neurobehavioral and Imaging Correlates of Hippocampal Atrophy in a Mouse Model of Vascular Cognitive Impairment. / Zuloaga, Kristen L.; Zhang, Wenri; Yeiser, Lauren A.; Stewart, Blair; Kukino, Ayaka; Nie, Xiao; Roese, Natalie E.; Grafe, Marjorie; Pike, Martin; Raber, Jacob; Alkayed, Nabil.

In: Translational Stroke Research, Vol. 6, No. 5, 05.06.2015, p. 390-398.

Research output: Contribution to journalArticle

Zuloaga, Kristen L. ; Zhang, Wenri ; Yeiser, Lauren A. ; Stewart, Blair ; Kukino, Ayaka ; Nie, Xiao ; Roese, Natalie E. ; Grafe, Marjorie ; Pike, Martin ; Raber, Jacob ; Alkayed, Nabil. / Neurobehavioral and Imaging Correlates of Hippocampal Atrophy in a Mouse Model of Vascular Cognitive Impairment. In: Translational Stroke Research. 2015 ; Vol. 6, No. 5. pp. 390-398.
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