Molecular pathways: radiation-induced cognitive impairment.
Molecular pathways: radiation-induced cognitive impairment.
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DOI：
10.1158/1078-0432.ccr-11-2903
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发表时间：
2013-05-01
期刊：
影响因子：
--
通讯作者：
Robbins ME
中科院分区：
文献类型：
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作者：
Greene-Schloesser D;Moore E;Robbins ME
在美国，每年大约有20万患者接受部分或全脑照射治疗原发性或转移性脑癌。根据现代治疗标准，早期和延迟的辐射效应是短暂的和可逆的；然而，晚期放射效应（放射后≥6个月）仍然存在显著风险，导致进行性认知障碍。这些包括记忆、注意力和执行功能的功能缺陷，严重影响患者的生活质量。辐射引起的认知损伤的机制仍然不明确。传统上，血管和神经炎性胶质细胞克隆源性群体的辐射诱导改变被假设为辐射诱导的脑损伤的原因。最近，临床前研究集中在海马体上，海马体是大脑中两个成人神经发生的部位之一，在学习和记忆中起着重要作用。辐射破坏海马神经发生，改变神经元功能，诱发神经炎症。将神经元干细胞植入海马体可防止辐照后神经发生减少并改善认知。临床处方药物，包括PPAR α和γ激动剂，以及RAS阻滞剂，可以预防辐射诱导的神经炎症和认知障碍，而不依赖于神经发生的改善。将这些令人兴奋的发现应用于临床，有望改善接受放射治疗的脑肿瘤患者的生活质量。
Approximately 200,000 patients/year in the US will receive partial or whole brain irradiation for the treatment of primary or metastatic brain cancer. Early and delayed radiation effects are transient and reversible with modern therapeutic standards; yet late radiation effects (≥6 months postirradiation) remain a significant risk, resulting in progressive cognitive impairment. These include functional deficits in memory, attention, and executive function that severely affect the patient’s quality of life (QOL). The mechanisms underlying radiation-induced cognitive impairment remain ill defined. Classically, radiation-induced alterations in vascular and neuroinflammatory glial cell clonogenic populations were hypothesized to be responsible for radiation-induced brain injury. Recently, preclinical studies have focused on the hippocampus, one of two sites of adult neurogenesis within the brain, which plays an important role in learning and memory. Radiation ablates hippocampal neurogenesis, alters neuronal function, and induces neuroinflammation. Neuronal stem cells implanted into the hippocampus prevent the decrease in neurogenesis and improve cognition following irradiation. Clinically prescribed drugs, including PPAR α and γ agonists, as well as RAS blockers, prevent radiation-induced neuroinflammation and cognitive impairment independent of improved neurogenesis. Translating these exciting findings to the clinic offers the promise of improving the QOL of brain tumor patients who receive radiotherapy.