Vascular Dementia (Vascular Cognitive Impairment)

To model vascular dementia (vascular cognitive impairment) in mice we use the bilateral carotid artery stenosis (BCAS) technique. BCAS is a mouse model of chronic cerebral hypoperfusion in which the cerebral white matter is damaged without significant gray matter lesions. The BCAS model employs the technique of wrapping metal coils (ideally 0.18 mm in diameter) around both surgically exposed common carotid arteries, thereby inducing bilateral cerebral hypoperfusion (Wolf et 2017). The model has demonstrated good reproducibility of white matter lesions (WMLs) characterized by blood-brain barrier disruption, glial activation, oxidative stress and oligodendrocyte loss following chronic cerebral hypoperfusion (Shibata et a, 2004; Ben-Ari et al 2019). BCAS provides a powerful tool to study the impact of WMLs on cognition. Deficits in perceptual memory are evident after BCAS and show a correlation with WMLs (Ben-Ari et al 2019).

Effect of bilateral common carotid artery stenosis (BCAS) on common carotid artery blood flow measured by laser Doppler flowmeter (From Wolf et al 2017).

Bar graphs showing the effect of BCAS microsurgery on diffusion tensor imaging (DTI) parameters. For fractional anisotropy (FA): corpus callosum: t (8)=4.371, p=0.002, adjusted p value=0.011; anterior commissure: F (1, 8)=79.49, p < 0.01, adjusted p value=0.001. (From: Ben-Ari et al 2019).

References

Shibata M, Ohtani R, Ihara M, Tomimoto H. White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion. Stroke. 2004 Nov;35(11):2598-603. doi: 10.1161/01.STR.0000143725.19053.60. Epub 2004 Oct 7

Ben-Ari H, Lifschytz T, Wolf G, Rigbi A, Blumenfeld-Katzir T, Merzel TK, Koroukhov N, Lotan A, Lerer B. White matter lesions, cerebral inflammation and cognitive function in a mouse model of cerebral hypoperfusion. Brain Res. 2019 May 15;1711:193-201. doi: 10.1016/j.brainres.2019.01.017. Epub 2019 Jan 16.

Wolf G, Lotan A, Lifschytz T, Ben-Ari H, Kreisel Merzel T, Tatarskyy P, Valitzky M, Mernick B, Avidan E, Koroukhov N, Lerer B. Differentially severe cognitive effects of compromised cerebral blood flow in aged mice: Association with myelin degradation and microglia activation. Front Aging Neurosci. 2017 Jun 16;9:191. doi: 10.3389/fnagi.2017.00191. eCollection 2017.