Department of Neurosurgery, The University of Illinois at Chicago, Chicago, Illinois, USA.
Department of Medicine, The University of Illinois at Chicago, Chicago, Illinois, USA.
World Neurosurg. 2021 Jan;145:187-196. doi: 10.1016/j.wneu.2020.08.161. Epub 2020 Sep 2.
The development of curative treatment for glioblastoma has been extremely challenging. Chemotherapeutic agents that have seemed promising have failed in clinical trials. Drugs that can successfully target cancer cells within the brain must first traverse the brain interstitial fluid. Cerebral microdialysis (CMD) is an invasive technique in which interstitial fluid can be directly sampled. CMD has primarily been used clinically in the setting of head trauma and subarachnoid hemorrhage. Our goal was to review the techniques, principles, and new data pertaining to CMD to highlight its use in neuro-oncology. We conducted a literature search using the PubMed database and selected studies in which the investigators had used CMD in either animal brain tumor models or clinical trials. The references were reviewed for additional information. Studies of CMD have shown its importance as a neurosurgical technique. CMD allows for the collection of pharmacokinetic data on drug penetrance across the blood-brain barrier and metabolic data to characterize the response to chemotherapy. Although no complications have been reported, the current CMD technique (as with any procedure) has risks and limitations, which we have described in the present report. Animal CMD experiments have been used to exclude central nervous system drug candidates from progressing to clinical trials. At present, patients undergoing CMD have been monitored in the intensive care unit, owing to the requisite tethering to the apparatus. This can be expected to change soon because of advances in microminiaturization. CMD is an extremely valuable, yet underused, technique. Future CMD applications will have central importance in assessing drug delivery to tumor cells in vivo, allowing a pathway to successful therapy for malignant brain tumors.
胶质母细胞瘤的治疗方法一直极具挑战性。在临床试验中,看似有前途的化疗药物都失败了。能够成功靶向大脑内癌细胞的药物首先必须穿过脑间质液。脑微透析(CMD)是一种侵入性技术,可以直接采集间质液。CMD 主要在颅脑创伤和蛛网膜下腔出血的临床环境中使用。我们的目标是回顾与 CMD 相关的技术、原理和新数据,以突出其在神经肿瘤学中的应用。我们使用 PubMed 数据库进行了文献检索,并选择了研究人员在动物脑肿瘤模型或临床试验中使用 CMD 的研究。对参考文献进行了进一步的审查以获取更多信息。CMD 的研究表明了它作为神经外科技术的重要性。CMD 允许收集药物穿透血脑屏障的药代动力学数据和代谢数据,以表征对化疗的反应。尽管尚未报告任何并发症,但目前的 CMD 技术(与任何程序一样)存在风险和限制,我们在本报告中进行了描述。动物 CMD 实验已被用于将候选药物从中枢神经系统中排除在临床试验之外。目前,由于需要与仪器连接,接受 CMD 的患者在重症监护病房中接受监测。由于微缩化方面的进展,这种情况很快就会改变。CMD 是一种非常有价值但未被充分利用的技术。未来的 CMD 应用将在评估药物向体内肿瘤细胞的递送方面具有重要意义,为恶性脑肿瘤的成功治疗开辟了道路。