Occlusion of the anterior cerebral artery after gamma knife irradiation in a rat

Abstract

The anterior cerebral artery of rats was irradiated at the level of the circle of Willis by Gamma Knife with a maximum dose of 25, 50, or 100 Gy. Occlusion of the anterior cerebral artery was observed in one rat which was followed for 20 months after irradiation of 100 Gy. Cerebral infarction was found at the midline-frontal region and the cingulate gyrus. Arterial wall thickening with fibrosis, splitting of the internal elastic membrane, luminal organized thrombus, and migration of smooth muscle cells into the thrombus were observed. In the anterior cerebral artery, thrombus formation seemed to occur after the endothelial injury and this may play a prominent role for occlusion. In small arteries, various changes were observed in the irradiated tissue. These included fibrosis and thrombus, thickened smooth muscle layer, lymphocytic infiltration, and thickening of vessel wall with fibrosis and fibrinous thrombosis with leakage of fibrin into the surrounding tissue after different doses of radiation and at different observation times. These changes were comparable to the ordinary vascular response to injury including healing vasculitis and arteriosclerosis.

Pathogenesis and radiobiology of brain arteriovenous malformations: implications for risk stratification in natural history and posttreatment course

“…58 Available data regarding the biology of radiation-induced vascular obliteration result from observations in BAVM tissue resected after radiosurgical treatment 14,82 and in irradiated arteries in animal models. 8,49,70,77 Observations from BAVM tissue 14,82 have suggested that damaged endothelial cells shrink, detach from neighboring endothelial cells and basement membrane, and permit platelet infiltration with deposition of fibrin and hyaline. As these endothelial cells slough off over time, inhibition of smooth muscle cell proliferation is lost, and smooth muscle cell migration into the subintimal layer results in collagen deposition that thickens the subintima and adventitia, progressively narrowing the lumen and eventually occluding it.…”

“…8,49,58,70,77 Failed mitosis of irradiated endothelial cells, damaged by direct interactions with irradiating electrons and indirect free-radical byproducts, results in eventual apoptosis 26 and initiation of radiationinduced arteriopathy. As such, it is believed that the latency period of BAVM obliteration after SRS is dependent on the turnover rate of endothelial cells, which typically ranges on the order of a couple of months to a couple of years, since initiation of the arteriopathy only manifests once endothelial cells attempt mitosis.…”

“…As such, it is believed that the latency period of BAVM obliteration after SRS is dependent on the turnover rate of endothelial cells, which typically ranges on the order of a couple of months to a couple of years, since initiation of the arteriopathy only manifests once endothelial cells attempt mitosis. 26,49,58 Currently, the major disadvantage of SRS is the latency period before a BAVM might successfully become obliterated, during which time the patient remains unprotected against risk of new ICH. 91 Widespread variation in patient response to SRS treatment of BAVMs may be the result of varying degrees of endothelial cell turnover, which is known to be abnormal in BAVMs.…”

Angiographic, hemodynamic, and histological changes in an animal model of brain arteriovenous malformations treated with Gamma Knife radiosurgery

“…Reports of the effects of radiosurgery on normal vessels include a study of GKS on cat basilar artery 10 and on rat anterior cerebral artery. 5 Findings included intimal proliferation but no vessel occlusion except in 1 rat anterior cerebral artery 20 months after treatment with 100 Gy.…”

Tolerance of Arteries to Microplanar X-Ray Beams

“…The comparatively deleterious effects of radiation doses of up to a few hectograys delivered to arteries in the broad-beam mode have been described (12)(13)(14)(15).…”