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

新型生物反应器系统可测试脑积水条件下导管故障的机制。

• 批准号: 10667087
• 负责人: Leandro Castaneyra Ruiz
• 金额: $ 21.25万
• 依托单位: CHILDREN'S HOSPITAL OF ORANGE COUNTY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10667087
• 关键词: Adhesions; Air; Antibiotics; Astrocytes; Bioreactors; Bypass; Catheters; Cell Culture Techniques; Cell Membrane Permeability; Cells; Cephalic; Cerebral Ventricles; Cerebrospinal Fluid; Cerebrospinal fluid shunts procedure; Childhood; Clinical; Communicating Hydrocephalus; Cytopathology; Derivation procedure; Devices; Disease; Distal; Engineering; Failure; Foreign-Body Giant Cells; Hour; Hydrocephalus; Hydrogels; Impairment; In Vitro; Inflammation; Inflammatory; Intracranial Hypertension; Intracranial Pressure; Link; Lymphocyte; Measures; Neurosurgeon; Obstruction; Operative Surgical Procedures; Organ; Organ Culture Techniques; Pathologic; Pathology; Patients; Peritoneum; Play; Positioning Attribute; Predisposition; Process; Production; Proliferating; Pump; Reaction; Research; Role; Shunt Device; Silicon; Structure of choroid plexus; Symptoms; System; Testing; Tissues; Vascularization; Ventricular; absorption; biological systems; body system; clinically relevant; design; experience; experimental study; glial activation; immunocytochemistry; implantation; in vitro Model; migration; monitoring device; pediatric patients; pressure

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.

抽象的 70 年来，脑积水的主要治疗方法一直集中在脑脊液分流术 (CSF) 引流上， 其目的是释放增加的颅内压（ICP）。不幸的是，脑脊液分流故障 以不可接受的速度； 98% 的患者一生中都会出现分流失败，并伴有心室梗阻 导管是小儿脑积水失败的主要原因。因此，了解机制 对于小儿神经外科医生来说，分流阻塞的基础已经变得至关重要。目前，只有少数 测试心室导管的生物系统（生物反应器）。然而，这些生物反应器未能模仿 脑积水病理学，因为他们不考虑 ICP，这是分流术的主要症状 来治疗。迄今为止开发的生物反应器在细胞学上也受到限制，因为它们没有考虑心室 区 (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 ChP的激活和增殖在分流阻塞过程中发挥着基础性作用。为了测试这个 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。该生物反应器旨在测试不同心室导管中的细胞阻塞情况 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）验证我们的体外生物反应器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 阻塞的易感性并为神经外科医生提供有价值的临床信息。我们将使用最近的 开发了体外模型作为模拟脑积水细胞病理学的理想实验平台，并且 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，提供 全面了解脑积水情况下的脑室导管阻塞。