PENTOBARBITAL EFFECTS ON BRAIN DAMAGE BY FRACTIONATED WHOLE BRAIN RADIATION

戊巴比妥对分段全脑辐射造成的脑损伤的影响

• 批准号: 3782401
• 负责人: E H OLDFIELD
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3782401
• 关键词: Macaca mulatta; anesthesia; anesthetics; brain neoplasms; capillary bed; glia; histopathology; ketamine; magnetic resonance imaging; neoplasm /cancer radiation therapy; neuroendocrine system; neurons; nonhuman therapy evaluation; pentobarbital; postmortem; radiation therapy dosage; radiobiology

Radiation therapy remains the single most effective treatment for malignant brain tumors, but in many cases, toxicity to normal brain impedes therapeutic doses sufficient for local control to be achieved. A substantial effort has been directed toward overcoming the unfavorable side effects of brain tumor radiation therapy. Data from our institute and others indicate that the concomitant application of pentobarbital anesthesia during cerebral irradiation reduces the toxicity of the ionizing radiation. Although mechanisms of this phenomenon remain unclear, it seems to arise from general suppression of brain synaptic activity or metabolism. After baseline MRI scans of the brain and neuroendocrine testings, primates (Macaca mulatta) undergo whole brain X-irradiation in 10 daily fractions, 360 rads each, total dose of 3600 rads. The monkeys in the study group were anesthetized with pentobarbital during the irradiation whereas the animals in the control group received ketamine. Each group consists of 6 animals. Neuroendocrine testing and MRI scan follow-up studies are performed at 3, 6 12, 18 and 24 months after irradiation. Quantitative histology will be done on the capillary bed, glial and neuronal populations after sacrifice.

放射治疗仍然是唯一最有效的治疗方法 恶性脑瘤，但在许多情况下，对正常大脑的毒性 阻碍了足以实现局部控制的治疗剂量。一个 已经做出了巨大的努力来克服不利的 脑肿瘤放射治疗的副作用。 来自我们研究所和其他机构的数据表明，伴随而来的 戊巴比妥钠麻醉在脑照射中的应用 降低电离辐射的毒性。尽管其运行机制 这一现象尚不清楚，它似乎是由普遍的镇压引起的 大脑的突触活动或新陈代谢。 在对大脑进行基线核磁共振扫描和神经内分泌测试后， 灵长类动物(猕猴)每天接受10次全脑X射线照射 分割，每个360拉德，总剂量为3600拉德。森林里的猴子 研究组在照射过程中用戊巴比妥钠麻醉 对照组动物注射氯胺酮。每组 由6只动物组成。神经内分泌检测和MRI扫描随访 在照射后3、6、12、18和24个月进行研究。 定量组织学检查将在毛细血管床、神经胶质和 处死后神经元数量。