Cerebral atherosclerosis occurs spontaneously in homozygous WHHL rabbits

We demonstrated that selectively bred homozygous WHHL rabbits known to show hypercholesterolemia and severe coronary atherosclerosis also spontaneousl y develop cerebral atherosclerosis beginning at 9 months of age. These intr acranial lesions occurred in the absence of hypertension in 24 of 25 animal s at various sites. mainly along arteries at the base of the brain. No lesi ons were observed in penetrating arteries. Lesions were rich in smooth musc le cells and fibrous tissue, showing only rare fragmentation or disappearan ce of the internal elastic lamina. and only limited lipid deposition. Few m acrophages were observed in these lesions. No significant correlation was s een between severity of cerebral atherosclerosis and age. systolic blood pr essure (BP), serum total cholesterol, or triglyceride concentration. Xantho mas of the pia mater were observed in all 25 rabbits. Arterial findings wer e similar to those in human cerebral atherosclerosis. indicating that the c oronary atherosclerosis-prone homozygous WHHL rabbit represents the first a nimal model for spontaneous cerebral atherosclerosis. (C) 2001 Elsevier Sci ence Ireland Ltd. All rights reserved.