Effects of blood coagulation factor XIII on the development of experimental cerebral aneurysms in rats

Pathological and experimental studies have shown that cerebral aneurysms develop in part as a result of injury to the blood vessel wall. One of the peculiar aspects of aneurysm development is a defective proliferative or healing response to such injury. To examine this phenomenon, blood coagulation Factor XIII, which is known to enhance the healing process of wounds in general, was given to rats to induce experimental cerebral aneurysms. The rats were subjected to ligation of one common carotid artery and induction of hypertension, and were fed beta-aminoproprionitrile. Two weeks thereafter, Factor XIII was injected intravenously daily for 5 days (10 U/100 gm body weight/day). Twelve days after the start of Factor XIII injections, the rats were sacrificed and examined under light and electron microscopy. In seven of 12 bifurcations which developed small aneurysms, prominent intimal thickening was observed in the aneurysm lumen. In the most advanced cases, the aneurysm lumen was completely filled with proliferated smooth-muscle cells and collagen. In five of nine bifurcations that showed no aneurysm development, apparent intimal thickening was found at the site where aneurysms might be expected to grow. In the group of rats studied for induction of cerebral aneurysms but not given Factor XIII, none of 11 bifurcations with or without aneurysms showed such intimal thickening. The results indicated that the proliferative response at the sites of aneurysm development was modified by exogenous Factor XIII.