Treatment of Cerebral Edema using Ventricular Therapy

描述（由申请人提供）：脑水肿与外伤性脑损伤有关。所提出的干预措施的总体假设是，创伤性损伤后从大脑中去除的游离水将最大限度地减少脑水肿。方法：申请人建议完成一种用于减少脑水肿的创新导管的临床前开发。该导管的最初临床应用将是外伤性脑损伤，包括用水去除疗法（WRT）导管取代标准的脑室引流管，该导管可从CS中去除大量水，2)去除大量脑脊液（CSF）样本，3)监测颅内压。去除游离水会增加脑脊液的渗透压，理论上这将导致脑间质水的去除和营养物质交换的改善，从而改善脑灌注。I期研究表明，人类脑脊液渗透压随着创伤性脑损伤而增加，WRT导管可以以临床显著的速度从脑脊液中清除水分，从而改善离体羊脑组织中的水分运动。具体目的：(1)体外构建和测试WRT导管，满足人体研究需求。(2)在无损伤猪模型体内测试WRT导管。这些测试将确定设备在不同操作参数下的安全性。(3)在猪模型冷冻伤后，在体内使用心室WRT导管测量大脑的变化（压力和肿胀）和功能结局。将进行急性（6小时）和慢性（1周）随机对照损伤研究。意义：外伤性脑损伤和严重脑卒中后脑水肿是一种危及生命的疾病，在很大一部分患者中，常规治疗难以治愈。目前的治疗方法（如过度通气、渗透剂或低温）与严重的副作用相关，并且随着使用时间的延长而增加。二期目标的成功完成将使WRT导管的人体研究成为可能。

DESCRIPTION (provided by applicant): Cerebral edema is associated with traumatic brain injury. The overall HYPOTHESIS of the proposed intervention is that free water removed from the brain following traumatic injury will minimize cerebral edema. Approach: The applicant proposes to complete preclinical development of an innovative catheter for the reduction of cerebral edema. The initial clinical application of this catheter will be traumatic brain injury, and will involve replacing standard ventricular drains with Water Removal Therapy (WRT) catheters that 1) remove fee water from the CS, 2) remove bulk cerebral spinal fluid (CSF) samples, and 3) monitor intracranial pressure. Removal of water free will increase osmolarity of the CSF, which will theoretically result in removal of interstitial brain water and improved nutrient exchange, creating improved cerebral perfusion. Phase I studies have demonstrated that human CSF osmolarity increases with traumatic brain injury and WRT catheters can remove water from CSF at clinically significant rates that improves water movement in ex vivo ovine cerebral tissue. Specific Aims: (1) Build and test WRT catheters in vitro to meet human study requirements. (2) Test WRT catheters in vivo in a non-injury swine model. These tests will establish device safety under different operating parameters. (3) Measure cerebral changes (pressure and swelling) and functional outcome with ventricular WRT catheter treatment in vivo after cold freeze injury in swine model. Acute (6 hours) and chronic (1 week) randomized controlled injury studies will be undertaken. Significance: Cerebral edema after traumatic injury and severe stroke is a life threatening condition that is refractory to conventional treatments in a significant population of patients. Current treatments (i.e. hyperventilation, osmotic agents, or hypothermia) are associated with serious side effects that increase with prolonged use. Successful completion of Phase II aims will make human studies of WRT catheters possible.