School of Engineering, Deakin University, Geelong, Victoria 3216, Australia.
Division of Engineering, Mayo Clinic, Rochester, Minnesota 55905, United States.
ACS Chem Neurosci. 2024 Sep 4;15(17):3220-3227. doi: 10.1021/acschemneuro.4c00410. Epub 2024 Aug 18.
The unique architecture of the brain and the blood-brain barrier imposes challenges for the measurement of parenchyma-derived biomarkers that prevent sufficient understanding of transient neuropathogenic processes. One solution to this challenge is direct sampling of brain interstitial fluid via implanted microperfusion probes. Seeking to understand spatial limitations to microperfusion in the brain, we employed computational fluid dynamics modeling and empirical recovery of fluorescently labeled dextrans in an animal model. We found that dextrans were successfully recovered via microperfusion over a 6 h sampling period, especially at probes implanted 2 mm from the dextran infusion point relative to probes implanted 5 mm from the injection site. Experimental recovery was consistently around 1% of simulated, suggesting that this parameter can be used to set practical limits on the maximal tissue concentration of proteins measured in microperfusates and on the spatial domain sampled by our multimodal microperfusion probe.
大脑独特的结构和血脑屏障给源于实质组织的生物标志物的测量带来了挑战,这阻碍了人们对短暂神经发病过程的充分理解。解决这一挑战的一种方法是通过植入的微灌注探针直接采集脑间质液。为了了解脑内微灌注的空间局限性,我们在动物模型中采用计算流体动力学模型和荧光标记葡聚糖的经验恢复方法。我们发现,通过微灌注可以在 6 小时的采样期内成功回收葡聚糖,特别是在距葡聚糖输注点 2 毫米处植入的探针,而在距注射部位 5 毫米处植入的探针则不然。实验恢复率始终约为模拟值的 1%,这表明该参数可用于设置微灌注液中测量的蛋白质的最大组织浓度和我们的多模态微灌注探针所采样的空间域的实际限制。