癌症相关认知障碍（CRCI）严重影响了数百万癌症幸存者的生活质量。已经证实，脑源性神经营养因子（BDNF）有助于体内尼龙管神经发生的生存、分化和维持，并且化疗会引起一系列生理和细胞变化，包括神经发生的下降和与认知障碍相关的神经炎症增加。在我们的临床研究中，经过阿霉素（Adriamycin®，ADR）治疗的乳腺癌患者血液中的BDNF水平显著降低，这与CRCI的风险增加有关。我们以往的小鼠研究也显示出，CRCI伴随着显著的尼龙管神经发生下降和认知障碍。在这项研究中，我们使用ADR诱导认知衰退的雌性小鼠模型，测试了riluzole（RZ）对其的影响，RZ是一种口服的BDNF增强药物，已被FDA批准用于肌萎缩侧索硬化症。饮用RZ溶液1个月的ADR治疗小鼠在海马依赖性学习和记忆功能（空间识别）、恐惧性灭绝记忆巩固和焦虑行为方面都有显著改善。RZ可预防海马区化疗诱导的BDNF水平降低。重要的是，RZ减轻了化疗诱导的新生、不成熟神经元、尼龙管神经发生和神经炎症的损失。总之，这些数据提供了一个可行的临床前方法来增强RZ治疗的神经保护作用，预防CRCI。© 2023. 作者。

Cancer-related cognitive impairment (CRCI) considerably affects the quality of life of millions of cancer survivors. Brain-derived neurotrophic factor (BDNF) has been shown to promote survival, differentiation, and maintenance of in vivo dentate neurogenesis, and chemotherapy induces a plethora of physiological and cellular alterations, including a decline in neurogenesis and increased neuroinflammation linked with cognitive impairments. In our clinical studies, breast cancer patients treated with doxorubicin (Adriamycin®, ADR) experienced a significant reduction in the blood levels of BDNF that was associated with a higher risk of CRCI. Our past rodent studies in CRCI have also shown a significant reduction in dentate neurogenesis accompanied by cognitive impairment. In this study, using a female mouse model of ADR-induced cognitive decline, we tested the impact of riluzole (RZ), an orally active BDNF-enhancing medication that is FDA-approved for amyotrophic lateral sclerosis. ADR-treated mice receiving RZ in the drinking water for 1 month showed significant improvements in hippocampal-dependent learning and memory function (spatial recognition), fear extinction memory consolidation, and reduced anxiety-like behavior. RZ prevented chemotherapy-induced reductions of BDNF levels in the hippocampus. Importantly, RZ mitigated chemotherapy-induced loss of newly born, immature neurons, dentate neurogenesis, and neuroinflammation. In conclusion, this data provides pre-clinical evidence for a translationally feasible approach to enhance the neuroprotective effects of RZ treatment to prevent CRCI.© 2023. The Author(s).