A new clinically relevant model for intracranial atherosclerosis in rats

Introduction: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and, in particular, has been implicated as a leading cause of recurrent ischemic stroke. We developed a new rat model to study intracranial atherosclerosis.

Methods: Twelve-week-old male Sprague-Dawley rats were divided into a control (on a maintain diet) and a high-cholesterol group (on a daily 1% cholesterol diet) for up to 6 weeks. During the first two weeks, NG-nitro-L-arginine methylester (L-NAME, 3 mg/mL) was added to the drinking water in the high-cholesterol group to induce intimal changes making the rats susceptible to atherosclerosis. Blood lipids, including low-density lipoprotein (LDL), cholesterol (CHO), triglycerides (TG), and high-density lipoprotein (HDL), were measured after 3 and 6 weeks. Histological sections of the brains, including internal carotid artery (ICA), middle cerebral artery (MCA), and basilar artery (BA), were prepared to study intracranial artery morphometry and intimal thickening. The levels of CD68, an inflammatory marker, within the vessel walls as determined by immunohistochemistry were also measured.

Results: The high-cholesterol diet increased the levels of classic blood markers of atherosclerosis, LDL, CHO, and TG as well as decreased HDL, which became progressively more intensive with time. Rats showed increased intimal thickening in the ICA, MCA, and BA. This protocol also increased the levels of CD68 immunoreactivity within the vessel walls.

Conclusions: A rat model of intracranial atherosclerosis was effectively developed by high-cholesterol diet and L-NAME administration. This clinically relevant model would be beneficial for studying ICAS.