Methods and devices to assist and improve cerebrospinal fluid drainage

摘要 被称为脑积水的过度脑脊液积聚影响了大约100万人 所有年龄段的美国人，特别是儿童(每100,000人中有88人)和老年人(每100,000人中有175人) 人口。脑积水常见于中枢神经系统损伤后，如 蛛网膜下腔出血和创伤性脑损伤。脑脊液有许多重要的功能作用，包括 维持离子和pH平衡；清除废物；体液因素的分布；以及提供缓冲 对大脑来说。因此，脑脊液的动态平衡对于正常的大脑功能至关重要。有几条出口路线 已发现脑脊液流出，如蛛网膜颗粒、血管旁神经和颅旁神经 通路和脑膜淋巴管。在目前的项目中，我们将利用脑脊液流动的排水系统 减少脑积水，清除细胞代谢废物。研究表明，高达50%的脑脊液引流 通过大脑淋巴管，然后是颈部淋巴结。我们建议颈部的收缩 肌肉，通过压缩颈部瓣膜装备的淋巴管和结节，能够 加速脑脊液引流，清除脑脊液过剩和废物代谢物。我们的预赛 结果表明，电刺激颈部肌肉可降低颅内压，并 通过动态增强磁共振成像检测到加速脑脊液流动 (DCE-MRI)。该项目的主要目标是研究经皮电刺激对小鼠的影响 颈部肌肉加速脑脊液流动。我们将在体内监测颈部肌肉期间脑室内的颅内压变化 动态增强MRI和大分子技术在刺激、脑脊液分布和引流中的应用 使用荧光示踪剂和荧光成像清除。使用已知的脑积水模型，高岭土 在枕大池注射，我们将评估慢性肌肉刺激(EMS)对 T2加权解剖MRI显示脑室扩大。我们还将通过以下方式评估老鼠的整体健康状况 运动和单任务认知测试。该项目的成果将为癌症的治疗提供新的场所。 治疗脑积水和其他潜在的淋巴通路受损的神经系统疾病。

ABSTRACT Excessive accumulation of cerebrospinal flow (CSF) known as hydrocephalus affects about 1 million Americans of all ages, which is especially high in children (88 per 100,000) and older (175 per 100,000) populations. Hydrocephalus is frequently observed following central nervous system insults such as subarachnoid hemorrhage and traumatic brain injury. CSF has numerous important functional roles including maintenance of ionic and pH balance; waste removal; distribution of humoral factors; and providing a cushion for the brain. Thus, CSF homeostasis is critically important for normal brain function. Several exit routes for the CSF outflow have been identified, such as the arachnoid granulations, paravascular and paracranial nerves pathways and meningeal lymphatics. In the current project, we will leverage the drainage system of the CSF flow to decrease hydrocephalus and clear the cellular metabolic waste. Studies showed that up to 50% of CSF drains through the brain lymphatics and then the cervical lymph nodes. We propose that contraction of the neck muscles, by compressing the underlying cervical valve-equipped lymph vessels and nodes, is capable of accelerating CSF drainage resulting in the clearance of CSF excess and waste metabolites. Our preliminary results demonstrated that electrostimulation of the neck muscles decreases intracranial pressure (ICP), and accelerates cerebrospinal fluid flow, detected by dynamic contrast-enhancement magnetic resonance imaging (DCE-MRI). The main goal of this project is to investigate whether percutaneous electrostimulation of the mouse neck muscles accelerate CSF flow. We will monitor in vivo ICP changes in the ventricles during neck muscle stimulation, CSF distribution and drainage using dynamic contrast-enhancement MRI and macromolecule clearance using fluorescent tracers and fluorescent imaging. Employing known models of hydrocephalus, kaolin injection in the cisterna magna, we will evaluate the effects of chronic electromyostimulation (EMS) on the ventriculomegaly by T2-weighted anatomic MRI. We will also assess the overall well-being of the mice by locomotor and single-task cognitive test. The results of this project will provide new therapeutic venues for the treatment of hydrocephalus and potentially other neurological diseases in which glymphatic pathway is impaired.