Phillips P C, Thaler H T, Berger C A, Fleisher M, Wellner D, Allen J C, Rottenberg D A
Ann Neurol. 1986 Nov;20(5):583-9. doi: 10.1002/ana.410200505.
Intravenous high-dose methotrexate chemotherapy may produce acute, subacute, or chronic neurotoxicity in patients with cancer. Acute encephalopathies following high-dose methotrexate treatment are recognized with increasing frequency. This study describes a model of acute high-dose methotrexate neurotoxicity in the rat characterized by a profound dose-dependent depression of cerebral glucose metabolism in association with behavioral and electroencephalographic abnormalities. Alterations in the amino acid profile, similar to those described in cancer patients after high-dose methotrexate treatment, were observed in the absence of biochemical evidence of systemic organ toxicity. This model facilitates the study of the biochemical mechanisms of antifolate neurotoxicity in humans and permits the evaluation of potential therapeutic interventions.
静脉注射大剂量甲氨蝶呤化疗可能会使癌症患者产生急性、亚急性或慢性神经毒性。大剂量甲氨蝶呤治疗后出现急性脑病的情况越来越常见。本研究描述了一种大鼠急性大剂量甲氨蝶呤神经毒性模型，其特征为脑葡萄糖代谢出现严重的剂量依赖性抑制，并伴有行为和脑电图异常。在没有全身器官毒性生化证据的情况下，观察到氨基酸谱的变化，类似于癌症患者大剂量甲氨蝶呤治疗后所描述的变化。该模型有助于研究人类抗叶酸神经毒性的生化机制，并允许评估潜在的治疗干预措施。
