Asymmetric Carotid Stenosis Model Shows Sharper Cognitive Decline in Mice

A mouse study comparing two ways of narrowing the neck arteries that supply the brain has found that an asymmetric stenosis configuration produces earlier and more severe cognitive and sensorimotor impairment than the conventional symmetric model widely used to study chronic cerebral hypoperfusion. The work, published in Cellular and Molecular Neurobiology, compared a previously described asymmetric 0.16/0.18-mm bilateral common carotid artery stenosis (BCAS) configuration with the standard symmetric 0.18/0.18-mm configuration over a longitudinal, multimodal characterization.

Chronic cerebral hypoperfusion is considered a core pathological mechanism underlying vascular cognitive impairment and dementia, and BCAS models are among the most widely used experimental systems for studying hypoperfusion-related brain injury. The researchers argued that the conventional symmetric configuration may not fully capture certain patterns of heterogeneous cerebral hypoperfusion seen in human carotid artery disease, motivating a head-to-head comparison of the two setups.

The key behavioral finding was temporal: mice in the asymmetric group showed earlier and more severe spatial learning and memory impairment than mice in the symmetric group, along with more persistent sensorimotor deficits. The asymmetric configuration also induced persistent and lateralized cerebral hypoperfusion, reflecting the deliberately unequal stenosis applied to the two common carotid arteries.

Structural brain changes followed a similar pattern. Transmission electron microscopy revealed ultrastructural alterations of the blood-brain barrier as early as seven days after surgery in the asymmetric group, accompanied by increased endogenous IgG leakage in the hippocampal CA1 region, an indicator of barrier disruption. The authors note that these barrier changes appeared early in the disease course, preceding the more extensive tissue injury documented at later time points.

White matter was assessed with multiple complementary methods, including myelin basic protein immunofluorescence, Luxol fast blue staining, and transmission electron microscopy. All three approaches demonstrated more severe myelin and axonal abnormalities in the asymmetric group, consistent with the greater hypoperfusion burden produced by the tighter unilateral stenosis.

Gray matter injury also emerged in the asymmetric model, with progressive neuronal loss observed predominantly in the hippocampus and later involvement of cortical and striatal gray matter. In addition, the asymmetric group exhibited more pronounced astrocytic and microglial immunoreactivity, indicating a stronger glial inflammatory response in regions supplied by the compromised circulation.

Overall, the authors concluded that compared with the symmetric configuration, the asymmetric model was associated with greater glial immunoreactivity, more extensive tissue injury, and more severe behavioral impairments. They positioned the asymmetric configuration as a potential complementary experimental paradigm for exploring the mechanisms of chronic hypoperfusion-related pathological progression and for evaluating candidate therapeutic strategies.

One important caveat is stated explicitly in the article’s graphical abstract: because the two configurations differed in both stenosis symmetry and unilateral stenotic severity, the observed differences cannot be attributed specifically to stenotic asymmetry itself. The asymmetric model combines a tighter stenosis on one side with an asymmetric arrangement, so the contribution of each factor remains to be disentangled in future work.

The study is reported as original research and is available as an open-access article published on 8 October 2026, shared early to provide faster access to peer-reviewed, accepted research; the version is subject to further edits before the final Version of Record. As with all rodent model studies, the findings describe experimental pathology in mice and do not by themselves establish clinical outcomes in humans, but they offer researchers a new tool for probing how unequal carotid stenosis shapes the trajectory of hypoperfusion-induced brain injury.

Subject of Research: Comparison of asymmetric and symmetric mouse models of chronic cerebral hypoperfusion

Article Title: Comparative Longitudinal Characterization of Asymmetric and Symmetric BCAS Configurations Reveals Distinct Chronic Hypoperfusion Phenotypes

Article References: Han, M., Hou, L., Xiao, Y., Jiang, Y., Li, Y., Ni, M., Yu, J., Wang, J., & Yuan, H. (2026). Comparative Longitudinal Characterization of Asymmetric and Symmetric BCAS Configurations Reveals Distinct Chronic Hypoperfusion Phenotypes. Cellular and Molecular Neurobiology. https://doi.org/10.1007/s10571-026-01833-4

Image Credits: AI Generated

DOI: 10.1007/s10571-026-01833-4

Keywords: chronic cerebral hypoperfusion, BCAS, vascular cognitive impairment, blood-brain barrier, white matter injury, hippocampus, spatial learning, microglia, astrocytes, mouse model, carotid artery stenosis, neuronal loss