Recovery from the damage of cranial radiation modulated by memantine, an NMDA receptor antagonist, combined with hyperbaric oxygen therapy
Recovery from the damage of cranial radiation modulated by memantine, an NMDA receptor antagonist, combined with hyperbaric oxygen therapy
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DOI：
10.1093/neuonc/noac162
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发表时间：
2022-06-28
期刊：
影响因子：
15.9
通讯作者：
Ishiuchi, Shogo
中科院分区：
文献类型：
--
作者：
Hokama, Yohei;Nishimura, Masahiko;Ishiuchi, Shogo
背景放射治疗是中枢神经系统恶性肿瘤的重要治疗选择。然而，颅辐射诱导海马功能障碍和白色损伤;这导致认知功能障碍，并导致患者生活质量下降。通过N-甲基-D-天冬氨酸受体（NMDARs）的兴奋性谷氨酸信号传导在海马神经发生和大脑中少突胶质细胞的髓鞘形成中起着中心作用。方法我们提供了一种在癌症治疗过程中定量人类受试者活脑中神经发生的方法。本研究采用神经影像学方法，利用独创的行为任务，对脑功能障碍患者海马记忆通路进行了研究。结果用非竞争性NMDAR拮抗剂美金刚胺治疗，通过功能磁共振成像检测到海马模式分离网络的损伤。放射治疗前用美金刚胺对患者进行高压预处理，大部分逆转了白色物质损伤，这是通过基于区域的空间静态的全脑分析检测到的。神经调节结合高压氧治疗和美金刚在放疗期间的管理促进海马功能和白色物质的完整性的恢复，并改善接受颅脑放射治疗的患者更高的认知功能。结论本文所述的用于海马功能障碍的诊断和治疗干预的方法可用于恢复接受过颅辐射的患者所经历的一些认知下降。恢复的潜在机制是产生新的神经元，这增强了在模式分离网络中的功能，在大脑中，导致认知得分的增加，和恢复的微观结构完整性的白色物质束揭示了基于域的空间静态分析。
Background Radiotherapy is an important treatment option for central nervous system malignancies. However, cranial radiation induces hippocampal dysfunction and white matter injury; this leads to cognitive dysfunction, and results in a reduced quality of life in patients. Excitatory glutamate signaling through N-methyl-d-aspartate receptors (NMDARs) plays a central role both in hippocampal neurogenesis and in the myelination of oligodendrocytes in the cerebrum. Methods We provide a method for quantifying neurogenesis in human subjects in live brain during cancer therapy. Neuroimaging using originally created behavioral tasks was employed to examine human hippocampal memory pathway in patients with brain disorders. Results Treatment with memantine, a non-competitive NMDAR antagonist, reversed impairment in hippocampal pattern separation networks as detected by functional magnetic resonance imaging. Hyperbaric preconditioning of the patients just before radiotherapy with memantine mostly reversed white matter injury as detected by whole brain analysis with Tract-Based Spatial Statics. Neuromodulation combined with the administration of hyperbaric oxygen therapy and memantine during radiotherapy facilitated the restoration of hippocampal function and white matter integrity, and improved higher cognitive function in patients receiving cranial radiation. Conclusions The method described herein, for diagnosis of hippocampal dysfunction, and therapeutic intervention can be utilized to restore some of the cognitive decline experienced by patients who have received cranial radiation. The underlying mechanism of restoration is the production of new neurons, which enhances functionality in pattern separation networks in the hippocampi, resulting in an increase in cognitive score, and restoration of microstructural integrity of white matter tracts revealed by Tract-Based Spatial Statics Analysis.