Rescue of cognitive function following fractionated brain irradiation in a novel preclinical glioma model.
Rescue of cognitive function following fractionated brain irradiation in a novel preclinical glioma model.
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DOI：
10.7554/elife.38865
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发表时间：
2018-11-13
期刊：
影响因子：
7.7
通讯作者：
Gupta N
中科院分区：
文献类型：
--
作者：
Feng X;Liu S;Chen D;Rosi S;Gupta N
超过一半的长期脑肿瘤幸存者会出现不可逆的认知能力下降，严重影响他们的生活质量。然而，没有允许长期评估认知的临床前模型，并且没有改善患者认知缺陷的治疗。在这里，我们报告了一种新的胶质瘤小鼠模型，提供了可管理的肿瘤生长和可靠的评估认知功能的治疗后的方式。使用这个模型，我们发现分次全脑照射（fWBI），而不是肿瘤生长，导致记忆缺陷。在fWBI期间CSF-1 R的瞬时抑制可延长荷胶质瘤小鼠的存活并完全预防fWBI诱导的记忆缺陷。这一结果表明，可以探索在放疗期间抑制CSF-1 R作为一种方法，以改善将接受fWBI的患者的生存和认知结局。总之，目前的研究提供了一个强大的工具来研究放射性神经胶质瘤荷瘤动物的认知缺陷的概念证明。
More than half of long-term brain tumor survivors develop irreversible cognitive decline that severely affect their quality of life. However, there is no pre-clinical model that allows long-term assessment of cognition, and there is no treatment which ameliorates cognitive deficits in patients. Here, we report a novel glioma mouse model that offers manageable tumor growth and reliable assessment of cognitive functions in a post-treatment manner. Using this model, we found that fractionated whole-brain irradiation (fWBI), but not tumor growth, results in memory deficits. Transient inhibition of CSF-1R during fWBI prolongs survival of glioma-bearing mice and fully prevents fWBI-induced memory deficits. This result suggests that CSF-1R inhibition during radiotherapy can be explored as an approach to improve both survival and cognitive outcomes in patients who will receive fWBI. Taken together, the current study provides a proof of concept of a powerful tool to study radiation-induced cognitive deficits in glioma-bearing animals.