Device for Improving Outcomes Following Decompressive Hemicraniectomy for Stroke

改善中风去骨瓣减压术后预后的装置

• 批准号: 9766419
• 负责人: BYRON D. FORD
• 金额: $ 17.54万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9766419
• 关键词: Aftercare; Animals; Anti-inflammatory; Blood - brain barrier anatomy; Blood Vessels; Brain; Brain Edema; Brain Stem; Cause of Death; Cerebral Edema; Cerebrum; Contrast Media; Convection; Development; Devices; Diagnosis; Diffuse; Drug Kinetics; Edema; Effectiveness; Evaluation; Event; Exposure to; FDA approved; Fiber; Financial Hardship; Histologic; Hour; Human; Image; Individual; Infarction; Intervention; Intracranial Hypertension; Intracranial Pressure; Ischemic Stroke; Laboratories; Lead; Legal patent; Liquid substance; Magnetic Resonance Imaging; Malignant - descriptor; Middle Cerebral Artery Infarction; Middle Cerebral Artery Occlusion; Modeling; Motor Activity; Necrosis; Neuregulin 1; Neuregulins; Neurologic; Neurological outcome; Neuronal Injury; Optical Coherence Tomography; Patients; Rattus; Recovery; Review Literature; Severities; Stroke; Testing; Time; Tissues; United States; Water; Work; animal data; base; behavior test; brain tissue; clinically significant; cost; cytotoxic; design; disability; experience; foot; human data; improved; improved outcome; mortality; neurorestoration; novel; off-patent; prevent; stroke model; stroke patient; uptake; vasogenic edema

Late diagnosed ischemic stroke is a leading cause of serious long-term disability and the 5th leading cause of death in the United States (U.S.). Ischemic stroke is often characterized by an early cytotoxic type of edema that occurs within minutes following ischemic followed by ionic edema caused by water uptake through the intact blood brain barrier (BBB). A vasogenic form of edema occurs hours later resulting from damage to the BBB which initiates a secondary wave of cytotoxic edema that leads to neuronal injury. Brain swelling (edema) and increased intracranial pressure is common among ischemic stroke patients. Clinically significant cerebral edema occurs frequently in patients with malignant middle cerebral artery infarction (MMI). Patients with MMI have a high mortality rate near 80%, primarily due to herniation and compression of the brain stem. At the extreme, about 10% of these patients experiencing MMI may be eligible for decompressive hemicraniectomy (DC). While DC can provide immediate relief of intracranial pressure due to edema, little else can be done and the patient is completely dependent on a natural rate of recovery. This proposal seeks to develop and test a novel device to reduce cerebral edema, improve neurological outcomes for MMI patients that undergo DC. The proposed work will be to ultimately design a topical osmotic therapy device (OTD, patent pending 20,130,115,267), specifically for DC for MMI patents to: 1) control cerebral edema, 2) stimulate an effective convective flux across tissue in eminent danger of damage near the necrotic core, and 3) deliver a neurorestorative agent, anti-inflammatory neuregulin (NRG-1) directly to the exposed cerebral tissue. This hollow-fiber based OTD will be in direct contact with the brain tissue after a DC, which enhances fluid and mass transfer in damaged tissues and reduces edema. Three specific aims will be pursued: (1) to develop and examine the efficacy of an OTD to reduce cerebral edema and induce mass transport in the tissue; (2) to evaluate the effectiveness of delivering NRG-1 at prescribed times and to determine if the combined strategy for reducing cerebral edema and delivering NRG-1 is as effective as the individual approaches; and (3) to evaluate the neurological outcomes following the use of the device. The proposed work will characterize the transport of fluids in cerebral tissues following application of this device after craniectomy in a middle cerebral artery occlusion (MCAO) animal ischemic stroke model. Optical coherence tomography (OCT) and magnetic resonance imaging (MRI) will be used to track edema within the cerebral tissues due to the OTD device in the absence and presence of treatment with NRG-1. Overall, this work has the potential to lead to a novel paradigm to reverse cerebral edema and improve neurological outcome for MMI patents who have undergone DC. If successful, this study would aid in the development of a new FDA-approved device for the treatment of ischemic stroke in humans.

迟到的缺血性中风是严重长期残疾的主要原因，是 美国死亡（美国）。缺血性中风通常以早期的细胞毒性水肿为特征 在缺血之后几分钟内发生，然后是由于通过水吸收引起的离子水肿 完整的血脑屏障（BBB）。几个小时后，由于对 BBB引发了导致神经元损伤的细胞毒性水肿的继发性波。脑肿胀（水肿） 颅内压增加在缺血性中风患者中很常见。临床意义的大脑 水肿经常发生在中大脑中动脉梗塞（MMI）的患者中。 MMI患者 高死亡率接近80％，这主要是由于脑干的催眠和压缩。在 极端，这些患有MMI的患者中约有10％可能有资格进行减压半骨切除术 （DC）。虽然DC可以立即由于水肿而立即减轻颅内压，但几乎没有其他事情可以做到，并且 患者完全取决于自然恢复率。该建议旨在开发和测试 减少脑水肿的新型装置，改善接受DC的MMI患者的神经系统效果。这 拟议的工作将最终设计局部渗透疗法（OTD，专利未决） 20,130,115,267），专门用于MMI专利的DC：1）控制脑水肿，2）刺激有效 对流横跨组织的通量在坏死核附近造成损害的显着危险，3）交付 神经探究剂，抗炎神经结合蛋白（NRG-1）直接对暴露的大脑组织。这 DC后，基于空心纤维的OTD将与脑组织直接接触，从而增强流体和 在受损组织中的传质并减少水肿。将追求三个具体目标：（1）开发和 检查OTD的功效减少脑水肿并诱导组织中的质量转运； （2）至 评估在规定时间交付NRG-1的有效性，并确定是否合并策略 用于减少脑水肿和递送NRG-1的方法与单个方法一样有效。 （3）到 使用设备后评估神经系统结果。拟议的工作将表征 颅骨切除术在中部大脑中使用该装置后，在脑组织中流体的运输 动脉阻塞（MCAO）动物缺血性中风模型。光学相干断层扫描（OCT）和磁性 共振成像（MRI）将用于跟踪由于OTD设备在脑组织内的水肿 NRG-1的缺乏和存在。总体而言，这项工作有可能导致小说 逆转大脑水肿的范式并改善了经过MMI专利的神经系统效果 DC。如果成功，这项研究将有助于开发新的FDA批准设备，以治疗 人类缺血性中风。