Mouse models of vascular cognitive impairment and dementia induced by carotid artery manipulations: current status

PURPOSE OF REVIEW: This review highlights three of the most promising mouse models of vascular cognitive impairment and dementia (VCID) that recapitulate chronic cerebral hypoperfusion. It also discusses therapeutic candidates evaluated using these models. RECENT FINDINGS: The three mouse models of chronic cerebral hypoperfusion induced by carotid artery manipulations are bilateral common carotid artery stenosis (BCAS), asymmetric common carotid artery surgery (ACAS), and gradual common carotid artery stenosis (GCAS). Altogether, these models reproduce white matter lesions and executive dysfunction. Notably, ACAS and GCAS exhibit gradual cerebral blood flow (CBF) reduction and motor impairments, addressing key limitations of BCAS, which induces abrupt CBF decrease and no motor deficits. Furthermore, ACAS uniquely demonstrates subcortical small infarcts, a hallmark feature of clinical VCID. These models have greatly contributed to elucidating VCID pathophysiology, including abnormal oligodendrocyte maturation, astrocytic dysfunction, and neuroinflammation. Several therapeutic strategies developed using these models - such as adrenomedullin and SIRT1 activator - are currently under investigation in clinical trials. SUMMARY: The three models are robust and complementary tools for exploring the VCID mechanisms. They have been instrumental in advancing our understanding of VCID pathogenesis and in facilitating the development of novel therapeutic approaches.