Radiosurgery-induced microvascular alterations precede necrosis of the brain neuropil.

Abstract

Radiosurgery is used as a therapeutic modality for a wide range of cerebral disorders. It is important to understand the underlying causes of deleterious side effects that may accompany gamma-irradiation of brain tissue. In this study, structural alterations in rat cerebral vessels subjected to gamma knife irradiation in vivo were examined, for elucidation of their potential role in necrosis formation. A maximal center dose of 75 Gy was delivered to the rat parietal cortex with a 4-mm collimator, and changes occurring before necrosis formation were assessed 3.5 months after irradiation. Transmission electron microscopy, using horseradish peroxidase as a tracer, and scanning electron microscopy with vascular casting were performed. The capillary network in the irradiated area exhibited thickening and vacuolation of the basement membrane. The capillary density in the irradiated area was lower and the average capillary diameter was larger, compared with the nonirradiated side. These results indicate that substantial changes in the neuropil do not occur 2 weeks before the time of definite necrosis formation, whereas changes in the basement membrane are prominent. The necrotic response to intermediate doses of focused-beam irradiation appears after a considerable latency period and then progresses rapidly. This contrasts with previously reported responses to fractionated whole-brain irradiation, in which damage occurs slowly and gradually. Alterations in the microvascular basement membrane precede overt cellular changes in neuronal and vascular cells and provide an early index of cerebrovascular dysfunction in regions destined to undergo necrosis.