Apolipoprotein E knockout rabbit model of intracranial atherosclerotic disease

Abstract

Intracranial atherosclerotic disease (ICAD) is the most common cause of stroke worldwide. [1][2][3] Pathophysiological mechanisms of ICAD have not been clarified in a way that is specific to intracranial disease, so current clinical management strategies are suboptimal.Better understanding of ICAD is needed through basic science and translational research to develop more effective treatment. A major hindrance in the study of ICAD pathophysiology is the lack of tissue for pathological evaluation, but this cannot be reliably obtained in humans. Biopsy is prohibitively morbid, so tissue is typically only obtained at autopsy. Given limitations in human investigation of ICAD, current management is based on extrapolation from extracranial disease. Such extrapolation may be flawed since intracranial and extracranial vessels arise from different germ cell layers, ectoderm, and mesoderm,

Rabbit models of intracranial atherosclerotic disease for pathological validation of vessel wall MRI

“…13 , 16 ApoE knockout has been used for disease investigation in a variety of species, and a rabbit strain that can be selectively bred was created in recent years. 17 , 18 , 29 , 30 This current investigation sought to evaluate such ApoE knockout rabbits against WHHL rabbits when evaluated with both vwMRI and histopathology. Both WHHL and ApoE knockout animals were found to harbor ICAD lesions.…”

“…16 Additional rabbit models of extracranial atherosclerosis exist, most notably using apolipoprotein E (ApoE) knockout rabbits, yet investigation for the development of intracranial atherosclerosis is lacking to date. 13 , 17 , 18 This study seeks to demonstrate the ability to perform vwMRI effectively in rabbits and assess the suitability of the ApoE knockout rabbit as a potential alternative to the WHHL model ICAD analysis, using histopathological correlation that is not available in human studies.…”

Spatially Resolved Transcriptomics for Evaluation of Intracranial Vessels in a Rabbit Model: Proof of Concept

“…There is a robust history of effective research performed using rabbits for investigation of cardiovascular diseases. (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) The current report describes the amenability of rabbits to SRT methods for next generation evaluation of cerebrovascular disorders. To our knowledge, this represents the first report of application of the Visium SRT platform to either rabbits or the intracranial circulation.…”

“…Euthanasia was performed in accordance with a protocol approved by the Institutional Animal Care and Use Committee and previously published. (18,25) General endotracheal anesthesia was induced with intramuscular injection of buprenorphine (0.03 mg/kg) followed later by a ketamine (25-35 mg/kg) and xylazine (3mg/kg) mixture. The fur of the pelvis was trimmed bilaterally.…”

“…(18–25) Additionally, their size allows for endovascular access to perform minimally invasive techniques, and absence of a rete mirabile allows for catheterization of the intracranial circulation, which cannot be achieved in most other large model animals. (25–31)…”