Zhang Chao, Feng Wei, Li Yusha, Kürths Jurgen, Yu Tingting, Semyachkina-Glushkovskaya Oxana, Zhu Dan
Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Britton Chance Center for Biomedical Photonics, Wuhan, Hubei, 430074, China.
MoE Key Laboratory for Biomedical Photonics, Collaborative Innovation Center for Biomedical Engineering, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
Lasers Surg Med. 2019 Sep;51(7):625-633. doi: 10.1002/lsm.23075. Epub 2019 Feb 27.
Photodynamic therapy (PDT), a minimally invasive therapeutic tool, has been an important option for post-surgical treatment of malignant gliomas (MGs) in both adult and young patients. Recent studies have shown that PDT can also open the blood-brain barrier (BBB). However, there are no optimized parameters of PDT for patients at different ages. To determine whether there are age differences in PDT effects on the BBB, we studied PDT-related BBB opening through the optical clearing skull window in healthy 4- and 8-week-old mice.
In this work, we realized BBB opening by combining PDT with the optical clearing skull window by using different radiant exposures (635 nm, 10-20-30-40 J/cm ) and 5-aminole-vulinic acid (5-ALA, 20 mg/kg). Then, we evaluated BBB permeability by: (i) spectrofluorimetric measuring of Evans Blue dye (EBd) leakage; (ii) confocal imaging of 70 kDa FITC-dextran extravasation and the BBB integrity; and (iii) histological analysis of brain tissues.
Using the skull optical clearing method, we demonstrated PDT-induced BBB opening to EBd and FITC-dextran in a radiant exposure manner. The histological analysis revealed the different severities of vasogenic edema corresponding to radiant exposures. Besides, the PDT-related increase in the BBB permeability to high weight molecules (EBd and FITC-dextran) and solutes (vasogenic edema) was more pronounced in 4-week-old mice than in 8-week-old mice.
The more pronounced PDT-induced BBB disruption in juvenile mice compared with adult mice suggests age differences in PDT-related BBB opening. This might be an important informative platform for a new application of PDT as a method for brain drug delivery, especially for post-surgical treatment of MGs. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
光动力疗法（PDT）是一种微创治疗工具，已成为成年和年轻患者恶性胶质瘤（MGs）术后治疗的重要选择。最近的研究表明，PDT还可以打开血脑屏障（BBB）。然而，对于不同年龄段的患者，尚无优化的PDT参数。为了确定PDT对BBB的影响是否存在年龄差异，我们通过光学透明颅骨窗对健康的4周龄和8周龄小鼠进行了与PDT相关的BBB开放研究。
在本研究中，我们通过使用不同的辐射剂量（635nm，10 - 20 - 30 - 40J/cm²）和5 - 氨基乙酰丙酸（5 - ALA，20mg/kg），将PDT与光学透明颅骨窗相结合来实现BBB开放。然后，我们通过以下方式评估BBB通透性：（i）荧光分光光度法测量伊文思蓝染料（EBd）泄漏；（ii）70kDa异硫氰酸荧光素 - 葡聚糖外渗和BBB完整性的共聚焦成像；以及（iii）脑组织的组织学分析。
使用颅骨光学透明方法，我们证明了PDT以辐射剂量方式诱导BBB对EBd和异硫氰酸荧光素 - 葡聚糖开放。组织学分析揭示了与辐射剂量相对应的血管源性水肿的不同严重程度。此外，与8周龄小鼠相比，4周龄小鼠中PDT相关的BBB对高分子量分子（EBd和异硫氰酸荧光素 - 葡聚糖）和溶质（血管源性水肿）的通透性增加更为明显。
与成年小鼠相比，幼年小鼠中PDT诱导的BBB破坏更为明显，这表明PDT相关的BBB开放存在年龄差异。这可能是PDT作为脑药物递送方法新应用的重要信息平台，特别是对于MGs的术后治疗。激光外科医学。©2019威利期刊公司
