Safety of tPA plus Transcranial Emission of Low-Energy Laser for Acute Stroke

有证据表明，低能量红外激光照射(LELI)可以改变许多疾病状态， 在临床前和临床研究中，我们已经开发出初步数据，表明中风是其中之一。 由于静脉注射组织型纤溶酶原激活剂(TPA)是目前FDA批准的唯一治疗急性 中风，但将症状的绝对解决率仅从25%提高到38%，有必要 进一步遏制或消除脑损伤的其他治疗方法。我们已经开发了一系列 动物脑缺血和出血模型，当以协调的方式使用时，应该有助于 找出Leli中与其作为辅助成分的可行性、安全性和有效性有关的许多重要变量 治疗以溶栓为主。为此，本项目旨在实现以下具体目标：(1) 使用兔小血栓脑栓塞模型(SCEM)研究Leli与tPA治疗的相互作用。 其允许监视行为端点。这种方法应该产生有助于预测的信息 乐力联合tPA在人类中的临床结果。这项研究还检查了是否有任何 乐力对大血栓栓塞模型(LCEM)中tPA诱导的脑出血的影响 用于警告或安抚临床研究人员关于Leli对中风患者的潜在副作用。(2) 进行II期临床试验，以测试乐力联合tPA的安全性和初步疗效 急性中风患者。 除溶栓外，中风治疗的一种方法是提供某种形式的神经保护。 卒中发作后立即减少因血流不足造成的损害，增加脑出血的时间窗 接受溶栓治疗的机会。第二种策略是在启动后进行神经保护 溶栓：在溶栓过程中减少损害。第三种是诱导神经保护 溶栓完全是为了挽救组织，否则即使血液流动已经恢复，组织也会死亡。 最后，制定恢复功能的策略将是有益的，至少可以恢复一些功能 神经功能。莱利有可能产生所有这些效果。这一政策的潜在影响 因此，急性中风疗法的研究成果意义深远。

There is evidence that low-energy infrared laser irradiation (LELI) can modify a number of disease states, and in preclinical and clinical studies we have developed preliminary data showing that stroke is among them. Since intravenous tissue plasminogen activator (tPA) is currently the only FDA-approved treatment for acute stroke, but increases the absolute rates of resolution of symptoms only from 25% to 38%, there is need for additional therapeutic modalities to further contain or eliminate brain damage. We have developed a series of animal cerebral ischemia and hemorrhage models that, when used in a coordinated fashion, should help identify many of the important variables in LELI that pertain to its viability, safety, and efficacy as an adjunctive therapy to thrombolysis. Toward this end, this project is designed to achieve the following specific aims: (1) Examine the interaction of LELI with tPA therapy using a rabbit small clot brain embolism model (SCEM), which allows monitoring of a behavioral endpoint. This approach should yield information that helps to predict the clinical outcome of LELI combined with tPA in humans. The study also examines whether there is any effect of LELI on tPA-induced intracerebral hemorrhaging in the large clot embolism model (LCEM), which will serve to warn or reassure clinical investigators about the potential of LELI side effects in stroke victims. (2) Conduct a phase II clinical trial to test safety and preliminarily assess efficacy of LELI in combination with tPA with acute stroke patients. One approach to stroke therapy, in addition to thrombolysis, is to provide some form of neuroprotection immediately after stroke onset to reduce the damage caused by lack of blood flow and increase the window of opportunity for thrombolytic therapy. A second strategy is to administer neuroprotection after initiation of thrombolysis to reduce damage while thrombolysis is occurring. A third is to induce neuroprotection after thrombolysis is complete to salvage tissue that would otherwise die even though blood flow has been restored. Finally, it would be useful to develop strategies to produce recovery of function that may restore at least some neurological function. LELI is potentially capable of producing all of these effects. The potential impact of the study results on acute stroke therapeutics is thus far-reaching.