Radiation-induced brain injury: A review.
Radiation-induced brain injury: A review.
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DOI：
10.3389/fonc.2012.00073
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发表时间：
2012
影响因子：
4.7
通讯作者：
Chan MD
中科院分区：
文献类型：
--
作者：
Greene-Schloesser D;Robbins ME;Peiffer AM;Shaw EG;Wheeler KT;Chan MD
在美国，每年约有100，000名原发性和转移性脑肿瘤患者存活足够长的时间（>6个月）以经历辐射诱导的脑损伤。在1970年之前，人类大脑被认为是高度放射抗性的;在单次剂量>30戈伊后发生急性中枢神经系统综合征;在分次剂量>60戈伊时发生白色坏死。虽然白色坏死在现代技术中并不常见，但功能缺陷，包括记忆、注意力和执行功能的进行性损伤已变得重要，因为它们对生活质量有深远的影响。临床前研究提供了宝贵的见解辐射引起的认知障碍的发病机制。鉴于其在记忆和神经发生中的核心作用，大多数这些研究都集中在海马体上。辐照儿童和年轻成年啮齿动物大脑导致几种海马变化，包括神经炎症和神经发生的显着减少。这些数据已被解释为表明，屏蔽海马将防止临床辐射诱导的认知障碍。然而，这种解释可能过于简单化。使用更接近成年人脑肿瘤群体的老年啮齿动物进行的研究表明，与儿童和年轻成年大鼠不同，老年大鼠未显示出辐射诱导的神经发生减少或成熟神经元丢失。然而，老年大鼠仍然表现出认知障碍。这发生在脱髓鞘和/或白色物质坏死的情况下，与临床观察到的情况相似，表明更微妙的分子、细胞和/或显微解剖学改变参与了这种辐射诱导的脑损伤。鉴于辐射引起的认知障碍可能反映海马和非海马依赖性结构域的损伤，迫切需要研究辐射在不同脑区的微观解剖和功能效应以及临床相关剂量和时间表的整合。最近开发的神经科学和神经影像学技术不仅提供了实现这一目标的机会，而且还提供了确定新的生物标志物和新的干预目标以预防或改善这些晚期效应的机会。
Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their integration at clinically relevant doses and schedules. Recently developed techniques in neuroscience and neuroimaging provide not only an opportunity to accomplish this, but they also offer the opportunity to identify new biomarkers and new targets for interventions to prevent or ameliorate these late effects.