Chemobrain as a Product of Growing Success in Chemotherapy - Focus on Glia as both a Victim and a Cure.

P. Walczak, M. Janowski
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引用次数: 23

Abstract

Chemotherapy-induced cognitive impairment or chemobrain is a frequent consequence of cancer treatment with many psychiatric features. Ironically, the increasing efficacy of chemotherapy leaves growing number of patients alive with chemobrain. Therefore, there is an urgent need for strategies capable of returning cancer survivors back to their pre-morbid quality of life. Molecular mechanisms of chemobrain are largely unknown. Over the last decade there was a lot of emphasis in preclinical research on inflammatory consequences of chemotherapy and oxidative stress but so far none of these approaches were translated into clinical scenario. The co-administration of chemotherapy with protective agents was evaluated preclinically but it should be introduced with caution as potential interference was not yet studied and that could blunt therapeutic efficacy. Stem cell-based regenerative medicine approach has so far been exploited very sparsely in the context of chemobrain and the focus was on indirect mechanisms or neuronal replacement in the hippocampus. However, there is evidence for widespread white matter abnormalities in patients with chemobrain. This is quite logical considering life-long proliferation and turnover of glial cells, which makes them vulnerable to chemotherapeutic agents. Feasibility of glia replacement has been established in mice with global dysmyelination where profound therapeutic effect has been observed but only in case of global cell engraftment (across the entire brain). While global glia replacement has been achieved in mice translation to clinical setting might be challenging due to much larger brain size. Therefore, a lot of attention should be directed towards the route of administration to accomplish widespread cell delivery. Techniques facilitating that broad cell distribution including intra-arterial and intrathecal methods should be considered as very compelling options. Summarizing, chemobrain is a rapidly growing medical problem and global glia replacement should be considered as worthwhile therapeutic strategy.
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化疗脑作为化疗日益成功的产物——关注神经胶质细胞既是受害者也是治愈者。
化疗引起的认知障碍或化学脑是具有许多精神特征的癌症治疗的常见后果。具有讽刺意味的是,化疗的效果越来越好,却让越来越多的患者存活下来。因此,迫切需要能够使癌症幸存者恢复其发病前生活质量的策略。化学脑的分子机制在很大程度上是未知的。在过去的十年中,有很多强调在临床前研究化疗和氧化应激的炎症后果,但到目前为止,这些方法都没有转化为临床场景。化疗与保护剂的联合使用在临床前进行了评估,但引入时应谨慎,因为潜在的干扰尚未研究,可能会降低治疗效果。到目前为止,基于干细胞的再生医学方法在化学脑的背景下很少被利用,重点是海马的间接机制或神经元替代。然而,有证据表明,在化学脑患者中存在广泛的白质异常。考虑到胶质细胞的终身增殖和周转,这使得它们容易受到化疗药物的影响,这是相当合乎逻辑的。神经胶质细胞替代的可行性已经在全脑髓鞘发育异常的小鼠中建立起来,在这种情况下观察到深刻的治疗效果,但只有在全脑细胞植入的情况下(整个大脑)。虽然已经在小鼠身上实现了全神经胶质细胞替代,但由于小鼠的大脑体积更大,将其转化为临床环境可能具有挑战性。因此,大量的注意力应该指向给药途径,以实现广泛的细胞递送。促进广泛细胞分布的技术,包括动脉内和鞘内方法,应该被认为是非常有说服力的选择。综上所述,化学脑是一个快速发展的医学问题,全球胶质细胞替代应被视为有价值的治疗策略。
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来源期刊
Neuropsychiatry
Neuropsychiatry NEUROSCIENCES-PSYCHIATRY
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>12 weeks
期刊介绍: Neuropsychiatry is a bimonthly, peer reviewed, open access Journal aimed at exploring the latest breakthroughs in brain and behavior in order to enhance our current understanding of the disturbances in brain function. The Journal has established itself among the most authoritative journals in the field by publishing cutting-edge research in neuropsychiatry and also serves as a forum for discussing the latest advancements and problem statements in the field.
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