Apolipoprotein E knockout rabbit model of intracranial atherosclerotic disease

Intracranial atherosclerotic disease (ICAD) is the most common cause of ischemic stroke. Poor understanding of the disease due to limited human data leads to imprecise treatment. Apolipoprotein E knockout (ApoE‐KO) rabbits were compared to an existing model, the Watanabe heritable hyperlipidemic (WHHL) rabbit, and wild‐type New Zealand white (NZW) rabbit controls. Intracranial artery samples were assessed on histopathology for the presence of ICAD. Logistic and ordinal regression analyses were performed to assess for disease presence and severity, respectively. Eighteen rabbits and 54 artery segments were analyzed. Univariate logistic analysis confirmed the presence of ICAD in model rabbits (P < .001), while no difference was found between WHHL and ApoE‐KO rabbits (P = .178). In multivariate analysis, only classification as a model vs wild‐type animal (P < .001) was associated with the presence of ICAD. Univariate ordinal regression analysis demonstrated an association between ICAD severity and model animals (P = .001), with no difference was noted between WHHL and ApoE‐KO rabbits (P = .528). In multivariate ordinal regression analysis, only classification as a model retained significance (P < .001). ICAD can be reliably produced in ApoE‐KO rabbits, developing the disease comparably to the older WHHL model. Further analysis is warranted to optimize accelerated development of ICAD in ApoE‐KO rabbits to more efficiently study this disease.