Device for Improving Outcomes Following Decompressive Hemicraniectomy for Stroke

晚期诊断的缺血性中风是导致严重长期残疾的主要原因，也是导致严重残疾的第五大原因 美国死亡人数(美国)。缺血性中风的特征通常是早期的细胞毒性水肿型。 这在缺血后几分钟内发生，随后是由于通过脑组织吸收水分而引起的离子性水肿 完整的血脑屏障(BBB)。血管源性的水肿会在数小时后发生，原因是 血脑屏障引发第二波细胞毒性水肿，导致神经元损伤。脑肿胀(浮肿) 在缺血性中风患者中，颅内压升高是很常见的。具有临床意义的脑部 恶性大脑中动脉梗死(MMI)患者常发生脑水肿。患有MMI的患者 死亡率很高，接近80%，主要是由于脑干突出和受压。在 极端情况下，这些接受MMI的患者中约有10%有资格接受去骨瓣减压术 (DC)。虽然DC可以立即缓解因浮肿引起的颅内压，但除此之外几乎没有什么办法。 病人完全依赖自然的恢复率。该提案旨在开发和测试一种 减少脑水肿，改善接受DC治疗的MMI患者的神经预后的新设备。这个 拟议的工作将是最终设计一种局部渗透疗法设备(OTD，正在申请专利 20,130,115,267)，专门针对DC的MMI专利：1)控制脑水肿，2)刺激有效 穿过组织的对流通量在坏死核附近有极大的损害危险，以及3)提供 神经恢复剂、抗炎神经调节素(NRG-1)直接作用于暴露的脑组织。这 基于中空纤维的OTD将在DC后与脑组织直接接触，这将增强液体和 在受损的组织中进行传质，减少浮肿。我们会追求三个具体目标：(1)发展 检查OTD在减少脑水肿和诱导组织内物质传输方面的有效性；(2) 评估在规定时间提供NRG-1的有效性，并确定联合战略是否 用于减轻脑水肿和传递NRG-1与个人方法一样有效；以及(3) 评估使用该设备后的神经学结果。拟议的工作将描述 中脑开颅术后应用该装置后脑组织中液体的转运 动脉闭塞(MCAO)动物缺血性卒中模型。光学相干层析成像(OCT)和磁学 磁共振成像(MRI)将被用来追踪由于OTD设备导致的脑组织内的水肿 没有或没有接受NRG-1治疗。总体而言，这项工作有可能导致一部小说 MMI患者治疗后逆转脑水肿和改善神经预后的范例 华盛顿特区。如果成功，这项研究将有助于开发FDA批准的治疗糖尿病的新设备 人类的缺血性中风。

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.