Pentoxifylline and Vitamin E Can Restrict Radiation Necrosis via Vascular Pathways, Experimental Study in an Animal Model

Abstract

Radiation necrosis is a long-term side effect of Gamma Knife stereotactic radiosurgery that may require surgical intervention. Pentoxifylline and vitamin E have previously been shown to be effective in the treatment of radiation necrosis in the published literature, but there are no data on the prophylactic use of these molecules or, more importantly, whether prophylaxis is required. The iatrogenic radiation necrosis model included 50 Sprague-Dawley rats of both sexes. There were seven treatment subgroups established. Gamma-Plan 8.32 was used to plan after magnetic resonance (MR) scans were performed in a specially designed frame. The injection doses used in the treatment groups were vitamin E (30 mg/kg/day in a single dose) and pentoxifylline (50 mg/kg/day in two doses). Control MR scans were performed at the end of a 16-week treatment, and the subjects were decapitated for pathological evaluations. The intensity of HIF-1α immunoreactivity is statistically significantly lower in the therapeutic vitamin E, prophylactic pentoxifylline and vitamin E, and therapeutic pentoxifylline and vitamin E groups than in the other groups. Similarly, the intensity of VEGF immunoreactivity was reduced in the therapeutic vitamin E and prophylactic pentoxifylline and vitamin E treatment modality groups. When compared with other groups, the therapeutic pentoxifylline group had significantly fewer VEGF-immunoreactive cells in the peri-necrotic area, with an accompanying decreased contrast enhancement pattern. Both vitamin E and pentoxifylline are effective for the treatment and/or restriction of radiation necrosis, either alone or in combination. The use of these molecules as a preventive measure did not outperform the therapeutic treatment.