通过使用 NMDA 受体拮抗剂美金刚联合高压氧治疗来调节颅辐射损伤的恢复。
Recovery from the damage of cranial radiation modulated by memantine, an NMDA receptor antagonist, combined with hyperbaric oxygen therapy.
机构信息
Department of Neurosurgery, Graduate School of Medicine, University of The Ryukyus, 207 Uehara, Nishihara-machi, Okinawa 903-0215, Japan.
出版信息
Neuro Oncol. 2023 Jan 5;25(1):108-122. doi: 10.1093/neuonc/noac162.
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.
背景
放射疗法是治疗中枢神经系统恶性肿瘤的重要手段之一。然而，颅部放射会导致海马功能障碍和白质损伤，从而导致认知功能障碍，降低患者的生活质量。通过 N-甲基-D-天冬氨酸受体（NMDAR）的兴奋性谷氨酸信号在海马神经发生和大脑中少突胶质细胞的髓鞘形成中都起着核心作用。
方法
我们提供了一种在癌症治疗过程中实时检测人脑内神经发生的方法。利用最初创建的行为任务进行神经影像学检查，以研究脑疾病患者的海马记忆通路。
结果
使用非竞争性 NMDAR 拮抗剂美金刚治疗可通过功能磁共振成像逆转海马模式分离网络的损伤。在接受放射治疗前对患者进行高压氧预处理，并用全脑分析的基于束流的空间统计学方法检测到白质损伤得到逆转。神经调节联合高压氧治疗和放射治疗期间使用美金刚可促进海马功能和白质完整性的恢复，提高接受颅部放射治疗的患者的高级认知功能。
结论
本文描述的用于诊断海马功能障碍和治疗干预的方法可用于恢复接受颅部放射治疗的患者所经历的部分认知下降。恢复的潜在机制是产生新的神经元，从而增强海马体中模式分离网络的功能，提高认知评分，并通过基于束流的空间统计学分析显示白质束的微观结构完整性得到恢复。
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