CEREBRAL RADIOPROTECTIVE EFFECTS OF HIGH-DOSE PENTOBARBITAL EVALUATEDIN AN ANIMAL RADIOSURGERY MODEL

Because pentobarbital has been shown to reduce cerebral toxicity to si ngle-fraction whole brain irradiation in a rat model, eve sought to ev aluate its cerebral radioprotective effects for stereotactic radiosurg ery. We hypothesized that concurrent high-dose pentobarbital anaesthes ia (50 mg kg(-1)) during irradiation could delay or prevent the onset of radiation necrosis within the radiosurgical volume. Six rats were p laced in pentobarbital or control groups, irradiated, and then evaluat ed 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 radioprot ective 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 n o 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 diffe rence between groups in observed blood vessel changes or nuclear chang es at any time interval (p > 0.6). There was no animal morbidity relat ed to radiosurgery. While pentobarbital may exhibit a radioprotective effect to lower dose, whole brain irradiation on a metabolic or cellul ar level, we could not identify any protective benefit for the prevent ion of focal radiation necrosis or other radiation-related histologic changes in this experiment. The model can be used to evaluate other po tential radioprotective agents, and to improve assessments of blood-br ain barrier integrity and ultrastructure.