Bender Tamara, Schickel Esther, Schielke Celine, Debus Jürgen, Grosshans David R, Durante Marco, Schroeder Insa S
GSI Helmholtzzentrum für Schwerionenforschung, Biophysics Department, Darmstadt, Germany.
Heidelberg University, Faculty of Medicine, and Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany.
Commun Biol. 2025 Feb 22;8(1):276. doi: 10.1038/s42003-025-07736-2.
Brain tumors are commonly treated with radiotherapy, but the efficacy of the treatment is limited by its toxicity to the normal tissue including post-irradiation contrast enhanced lesions often linked to necrosis. The poorly understood mechanisms behind such brain lesions were studied using cerebral organoids. Here we show that irradiation of such organoids leads to dose-dependent growth retardation and formation of liquid-filled cavities but is not correlated with necrosis. Instead, the radiation-induced changes comprise of an enhancement of cortical hem markers, altered neuroepithelial stem cell differentiation, and an increase of ZO1/AQP1/CLDN3-choroid plexus (CP)-like structures accompanied by an upregulation of IGF2 mRNA, known to be expressed in CP and cerebrospinal fluid. The altered differentiation is attributed to changes in the WNT/BMP signaling pathways. We conclude that aberrant CP formation can be involved in radiation-induced brain lesions providing additional strategies for possible countermeasures.
脑肿瘤通常采用放射治疗，但该治疗的疗效受到其对正常组织毒性的限制，包括照射后常与坏死相关的对比增强病变。利用脑类器官研究了此类脑损伤背后尚未完全了解的机制。在这里，我们表明，对此类类器官进行照射会导致剂量依赖性生长迟缓并形成充满液体的腔，但与坏死无关。相反，辐射诱导的变化包括皮质下标志物增强、神经上皮干细胞分化改变，以及ZO1/AQP1/CLDN3-脉络丛（CP）样结构增加，同时伴有IGF2 mRNA上调，已知其在CP和脑脊液中表达。分化改变归因于WNT/BMP信号通路的变化。我们得出结论，异常的CP形成可能与辐射诱导的脑损伤有关，为可能的应对措施提供了额外的策略。
