Cerebral radioprotective effects of high-dose pentobarbital evaluated in an animal radiosurgery model

Because pentobarbital has been shown to reduce cerebral toxicity to single-fraction whole brain irradiation in a rat model, we sought to evaluate its cerebral radioprotective effects for stereotactic radiosurgery. We hypothesized that concurrent high-dose pentobarbital anaesthesia (50 mg kg-1) during irradiation could delay or prevent the onset of radiation necrosis within the radiosurgical volume. Six rats were placed in pentobarbital or control groups, irradiated, and then evaluated at different intervals (60, 100, 150, 365 days; total = 48 animals studied). All rats had 100 Gy radiosurgery to the right frontal brain region (a threshold dose for focal necrosis at 90 days). The radioprotective effects of pentobarbital were compared to ketamine anaesthesia (control) and evaluated for observed focal necrosis, size of necrotic lesion, blood vessel alterations, and to changes in cell nuclei. There was no difference between groups in the numbers of rats with necrosis at 100 days (p = 0.72), at 150 days (p = 0.77), or at 365 days (p = 0.77); no necrosis was observed in either group at 60 days. There was no difference in the size of the necrotic lesion at 100 days (p = 1.0), at 150 days (p = 0.39), or at 365 days (p = 0.07). There was no difference between groups in observed blood vessel changes or nuclear changes at any time interval (p > 0.6). There was no animal morbidity related to radiosurgery.(ABSTRACT TRUNCATED AT 250 WORDS)