Device for Improving Outcomes Following Decompressive Hemicraniectomy for Stroke

晚期诊断的缺血性卒中是导致严重长期残疾的主要原因，也是第五大导致 死亡在美国（美国）。缺血性中风通常以早期细胞毒性水肿为特征 在缺血后几分钟内发生，随后是由水通过血管吸收引起的离子性水肿。 完整血脑屏障（BBB）。血管源性水肿在数小时后发生，这是由于 血脑屏障，引发细胞毒性水肿的第二波，导致神经元损伤。脑肿胀（水肿） 并且颅内压升高在缺血性中风患者中是常见的。具有临床意义的脑部 脑水肿是恶性大脑中动脉梗塞（MMI）患者的常见症状。MMI患者 有近80%的高死亡率，主要是由于脑疝和压迫脑干。在 极端情况下，大约10%的患有MMI的患者可能适合进行减压性半颅骨切除术 （DC）。虽然DC可以立即缓解由于水肿引起的颅内压，但几乎没有其他方法， 病人完全依赖于自然恢复率。该提案旨在开发和测试一种 一种新型器械，可减少脑水肿，改善接受DC治疗的MMI患者的神经功能结局。的 建议的工作将是最终设计一种局部渗透治疗装置（OTD，专利申请中 20，130，115，267），专门用于MMI专利的DC：1）控制脑水肿，2）刺激有效的 穿过坏死核心附近具有显著损伤危险的组织的对流通量，以及3）递送 将神经修复剂、抗炎神经调节蛋白（NRG-1）直接施用至暴露的脑组织。这 基于中空纤维的OTD将在DC之后与脑组织直接接触，这增强了流体和 在受损组织中进行质量转移并减少水肿。将追求三个具体目标：（1）发展和 检查OTD减轻脑水肿和诱导组织中物质转运的功效;（2） 评估在规定时间内交付NRG-1的有效性，并确定联合战略是否 用于减少脑水肿和递送NRG-1与个体方法一样有效;和（3） 评价使用器械后的神经系统结局。拟议的工作将突出 中脑颅骨切除术后应用该装置后脑组织中的液体运输 动脉闭塞（MCAO）动物缺血性中风模型。光学相干断层扫描（OCT）和磁共振成像（MRI） 共振成像（MRI）将用于跟踪脑组织内由于OTD装置引起的水肿。 不存在和存在NRG-1治疗。总的来说，这部作品有可能成为一部小说。 逆转脑水肿并改善接受MMI治疗的患者的神经功能结局的范例 DC.如果成功的话，这项研究将有助于开发一种新的FDA批准的用于治疗 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.