Radiosurgery-induced microvascular alterations precede necrosis of the brain neuropil

OBJECTIVE: 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 t issue. In this study, structural alterations in rat cerebral vessels subjec ted to gamma knife irradiation in vivo were examined, for elucidation of th eir potential role in necrosis formation. METHODS: A maximal center dose of 75 Gy was delivered to the rat parietal c ortex with a 4-mm collimator, and changes occurring before necrosis formati on were assessed 3.5 months after irradiation. Transmission electron micros copy, using horseradish peroxidase as a tracer, and scanning electron micro scopy with vascular casting were performed. RESULTS: The capillary network in the irradiated area exhibited thickening and vacuolation of the basement membrane. The capillary density in the irra diated area was lower and the average capillary diameter was larger, compar ed with the nonirradiated side. These results indicate that substantial cha nges in the neuropil do not occur 2 weeks before the time of definite necro sis formation, whereas changes in the basement membrane are prominent. CONCLUSION: The necrotic response to intermediate doses of focused-beam irr adiation appears after a considerable latency period and then progresses ra pidly. This contrasts with previously reported responses to fractionated wh ole-brain irradiation, in which damage occurs slowly and gradually. Alterat ions in the microvascular basement membrane precede overt cellular changes in neuronal and vascular cells and provide an early index of cerebrovascula r dysfunction in regions destined to undergo necrosis.