Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Department of Neurosurgery, Hospices Civils de Lyon, Bron, France.
J Neurooncol. 2024 Aug;169(1):1-10. doi: 10.1007/s11060-024-04719-x. Epub 2024 Jun 4.
Understanding the complex bidirectional interactions between neurons and glioma cells could help to identify new therapeutic targets. Herein, the techniques and application of novel neuroscience tools implemented to study the complex interactions between brain and malignant gliomas, their results, and the potential therapeutic opportunities were reviewed.
Literature search was performed on PubMed between 2001 and 2023 using the keywords "glioma", "glioblastoma", "circuit remodeling", "plasticity", "neuron networks" and "cortical networks". Studies including grade 2 to 4 gliomas, diffuse midline gliomas, and diffuse intrinsic pontine gliomas were considered.
Glioma cells are connected through tumour microtubes and form a highly connected network within which pacemaker cells drive tumorigenesis. Unconnected cells have increased invasion capabilities. Glioma cells are also synaptically integrated within neural circuitry. Neurons promote tumour growth via paracrine and direct electrochemical mechanisms, including glutamatergic AMPA-receptors. Increased glutamate release in the tumor microenvironment and loss of peritumoral GABAergic inhibitory interneurons result in network hyperexcitability and secondary epilepsy. Functional imaging, local field potentials and subcortical mapping, performed in awake patients, have defined patterns of malignant circuit remodeling. Glioma-induced remodeling is frequent in language and even motor cortical networks, depending on tumour biological parameters, and influences functional outcomes.
These data offer new insights into glioma tumorigenesis. Future work will be needed to understand how tumor intrinsic molecular drivers influence neuron-glioma interactions but also to integrate these results to design new therapeutic options for patients.
了解神经元和神经胶质瘤细胞之间复杂的双向相互作用有助于确定新的治疗靶点。本文综述了应用新型神经科学工具研究脑与恶性神经胶质瘤之间复杂相互作用的技术和应用、研究结果以及潜在的治疗机会。
在 2001 年至 2023 年期间，使用“glioma”、“glioblastoma”、“circuit remodeling”、“plasticity”、“neuron networks”和“cortical networks”等关键词在 PubMed 上进行文献检索。考虑了包括 2 级至 4 级神经胶质瘤、弥漫性中线神经胶质瘤和弥漫性内在脑桥神经胶质瘤在内的研究。
神经胶质瘤细胞通过肿瘤微管连接，并在其中形成高度连接的网络，起搏细胞驱动肿瘤发生。未连接的细胞具有更高的侵袭能力。神经胶质瘤细胞也在神经回路中形成突触连接。神经元通过旁分泌和直接电化学机制促进肿瘤生长，包括谷氨酸 AMPA 受体。肿瘤微环境中谷氨酸释放增加和肿瘤周围 GABA 能抑制性中间神经元丢失导致网络过度兴奋和继发癫痫。在清醒患者中进行的功能成像、局部场电位和皮质下映射，定义了恶性回路重塑的模式。神经胶质瘤诱导的重塑在语言甚至运动皮质网络中很常见，这取决于肿瘤的生物学参数，并影响功能结局。
这些数据为神经胶质瘤的肿瘤发生提供了新的见解。未来需要进一步研究肿瘤内在分子驱动因素如何影响神经元-神经胶质瘤相互作用，以及如何整合这些结果来为患者设计新的治疗选择。
