New Bioreactor System to Test the Mechanisms that Underlay Catheter Malfunction Under Hydrocephalic Conditions.

摘要 70年来，脑积水的主要治疗集中在脑脊液分流（CSF）衍生， 其被执行以释放增加的颅内压（ICP）。不幸的是脑脊液分流器故障 以不可接受的比率; 98%的患者在其一生中遭受分流失败，伴有心室阻塞 导管是小儿脑积水失败的主要原因。因此，了解这些机制 这对小儿神经外科医生来说是至关重要的。目前，只有少数 测试脑室导管的生物系统（生物反应器）。然而，这些生物反应器未能模拟生物反应器的生物学特性。 脑积水病理学，因为他们没有考虑ICP，这是分流术的主要症状 迄今为止开发的生物反应器也受到细胞学的限制，因为它们不考虑心室 带（VZ）细胞或脉络丛（ChP）。因此，我们的中心假设是炎症依赖性VZ神经胶质细胞 激活和ChP增殖在分流阻塞的过程中起基本作用。为了验证这一 假设，我们的小组正在开发一种独特的体外生物反应器，模拟细胞病理学， 脑积水该生物反应器设计用于在以下条件下测试不同脑室导管中的细胞阻塞 正常和病理条件下，具有调节压力和导管流量的能力。三个具体目标 将检验这一假设：（1）将体外生物反应器用于在常压条件下测试导管;（2） 在高压条件下测试我们的体外生物反应器;（3）测试可用的近端导管， 并为神经外科医生提供有价值的临床信息。我们将利用我们最近 建立了体外模型，为模拟脑积水细胞病理学提供了理想的实验平台， 我们将利用我们在ChP器官培养方面的经验，结合这种独特的生物反应器， 全面了解脑积水条件下脑室导管阻塞。

ABSTRACT For 70 years, the primary treatment for hydrocephalus has focused on cerebrospinal fluid shunt (CSF) derivation, which is performed to release the increased intracranial pressure (ICP). Unfortunately, CSF shunts malfunction at an unacceptable rate; 98% of patients suffer shunt failure in their lifetime, with obstruction of the ventricular catheter as the leading cause of failure in pediatric hydrocephalus. Therefore, understanding the mechanisms that underlie shunt blockage has become essential for pediatric neurosurgeons. Currently, there are only a few biological systems (bioreactors) that test ventricular catheters. However, these bioreactors fail to mimic the hydrocephalic pathology since they do not consider ICP, which is the main symptom that the shunts are meant to treat. The bioreactors developed to date are also cytologically limited since they do not consider ventricular zone (VZ) cells or choroid plexus (ChP). Thus, our central hypothesis is that inflammatory-dependent VZ glial activation and ChP proliferation play a fundamental role in the process of shunt obstruction. To test this hypothesis, our group is developing a unique in vitro bioreactor that mimics the cytopathology of hydrocephalus. The bioreactor is designed to test cellular obstruction in different ventricular catheters under normal and pathological conditions, with the capacity to modulate pressure and catheter flow. Three specific aims will test this hypothesis: (1) Validate our in vitro bioreactor to test catheters in normal-pressure conditions; (2) Test our in vitro bioreactor under high-pressure conditions; (3) Test available proximal catheters for susceptibility to obstruction and provide valuable clinical information to neurosurgeons. We will use our recently developed in vitro model as an ideal experimental platform to mimic the cytopathology of hydrocephalus, and we will leverage our experience with ChP organ cultures, in combination with this unique bioreactor, to provide a comprehensive understanding of ventricular catheter obstruction under hydrocephalic conditions.