Skip to main content
Erschienen in: Translational Stroke Research 5/2015

01.10.2015 | Original Article

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

verfasst von: 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

Erschienen in: Translational Stroke Research | Ausgabe 5/2015

Einloggen, um Zugang zu erhalten

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.
Literatur
2.
Zurück zum Zitat Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke J Cereb Circ. 2011;42(9):2672–713. doi:10.1161/STR.0b013e3182299496.CrossRef Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke J Cereb Circ. 2011;42(9):2672–713. doi:10.​1161/​STR.​0b013e3182299496​.CrossRef
4.
Zurück zum Zitat Yoshizaki K, Adachi K, Kataoka S, Watanabe A, Tabira T, Takahashi K, et al. Chronic cerebral hypoperfusion induced by right unilateral common carotid artery occlusion causes delayed white matter lesions and cognitive impairment in adult mice. Exp Neurol. 2008;210(2):585–91. doi:10.1016/j.expneurol.2007.12.005.CrossRefPubMed Yoshizaki K, Adachi K, Kataoka S, Watanabe A, Tabira T, Takahashi K, et al. Chronic cerebral hypoperfusion induced by right unilateral common carotid artery occlusion causes delayed white matter lesions and cognitive impairment in adult mice. Exp Neurol. 2008;210(2):585–91. doi:10.​1016/​j.​expneurol.​2007.​12.​005.CrossRefPubMed
7.
Zurück zum Zitat Bink DI, Ritz K, Aronica E, van der Weerd L, Daemen MJ. Mouse models to study the effect of cardiovascular risk factors on brain structure and cognition. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 2013;33(11):1666–84. doi:10.1038/jcbfm.2013.140.CrossRef Bink DI, Ritz K, Aronica E, van der Weerd L, Daemen MJ. Mouse models to study the effect of cardiovascular risk factors on brain structure and cognition. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 2013;33(11):1666–84. doi:10.​1038/​jcbfm.​2013.​140.CrossRef
9.
Zurück zum Zitat Fuchtemeier M, Brinckmann MP, Foddis M, Kunz A, Po C, Curato C, et al. Vascular change and opposing effects of the angiotensin type 2 receptor in a mouse model of vascular cognitive impairment. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 2014. doi:10.1038/jcbfm.2014.221. Fuchtemeier M, Brinckmann MP, Foddis M, Kunz A, Po C, Curato C, et al. Vascular change and opposing effects of the angiotensin type 2 receptor in a mouse model of vascular cognitive impairment. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 2014. doi:10.​1038/​jcbfm.​2014.​221.
11.
Zurück zum Zitat Benice TS, Raber J. Object recognition analysis in mice using nose-point digital video tracking. J Neurosci Methods. 2008;168(2):422–30. Benice TS, Raber J. Object recognition analysis in mice using nose-point digital video tracking. J Neurosci Methods. 2008;168(2):422–30.
12.
Zurück zum Zitat Anagnostaras SG, Wood SC, Shuman T, Cai DJ, LeDuc AD, Zurn KR et al. Automated assessment of Pavlovian conditioned freezing and shock reactivity in mice using the VideoFreeze system. Front Behav Neurosci. 2010;4. doi:10.3389/fnbeh.2010.00158. Anagnostaras SG, Wood SC, Shuman T, Cai DJ, LeDuc AD, Zurn KR et al. Automated assessment of Pavlovian conditioned freezing and shock reactivity in mice using the VideoFreeze system. Front Behav Neurosci. 2010;4. doi:10.​3389/​fnbeh.​2010.​00158.
13.
Zurück zum Zitat Ostergaard L, Weisskoff R, Chesler D, Gyldensted C. High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part I: mathematical approach and statistical analysis. MRM. 1996;36:715–25.CrossRefPubMed Ostergaard L, Weisskoff R, Chesler D, Gyldensted C. High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part I: mathematical approach and statistical analysis. MRM. 1996;36:715–25.CrossRefPubMed
14.
Zurück zum Zitat Pike MM, Stoops CN, Langford CP, Akella NS, Nabors LB, Gillespie GY. High-resolution longitudinal assessment of flow and permeability in mouse glioma vasculature: sequential small molecule and SPIO dynamic contrast agent MRI. Magn Reson Med. 2009;61(3):615–25. doi:10.1002/mrm.21931.PubMedCentralCrossRefPubMed Pike MM, Stoops CN, Langford CP, Akella NS, Nabors LB, Gillespie GY. High-resolution longitudinal assessment of flow and permeability in mouse glioma vasculature: sequential small molecule and SPIO dynamic contrast agent MRI. Magn Reson Med. 2009;61(3):615–25. doi:10.​1002/​mrm.​21931.PubMedCentralCrossRefPubMed
16.
Zurück zum Zitat Fotuhi M, Do D, Jack C. Modifiable factors that alter the size of the hippocampus with ageing. Nat Rev Neurol. 2012;8(4):189–202.PubMed Fotuhi M, Do D, Jack C. Modifiable factors that alter the size of the hippocampus with ageing. Nat Rev Neurol. 2012;8(4):189–202.PubMed
17.
Zurück zum Zitat Toyama K, Koibuchi N, Uekawa K, Hasegawa Y, Kataoka K, Katayama T, et al. Apoptosis signal-regulating kinase 1 is a novel target molecule for cognitive impairment induced by chronic cerebral hypoperfusion. Arterioscler Thromb Vasc Biol. 2014;34(3):616–25. doi:10.1161/ATVBAHA.113.302440.CrossRefPubMed Toyama K, Koibuchi N, Uekawa K, Hasegawa Y, Kataoka K, Katayama T, et al. Apoptosis signal-regulating kinase 1 is a novel target molecule for cognitive impairment induced by chronic cerebral hypoperfusion. Arterioscler Thromb Vasc Biol. 2014;34(3):616–25. doi:10.​1161/​ATVBAHA.​113.​302440.CrossRefPubMed
18.
Metadaten
Titel
Neurobehavioral and Imaging Correlates of Hippocampal Atrophy in a Mouse Model of Vascular Cognitive Impairment
verfasst von
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
Publikationsdatum
01.10.2015
Verlag
Springer US
Erschienen in
Translational Stroke Research / Ausgabe 5/2015
Print ISSN: 1868-4483
Elektronische ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-015-0412-z

Weitere Artikel der Ausgabe 5/2015

Translational Stroke Research 5/2015 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Neu im Fachgebiet Neurologie

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.