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。 由于静脉内组织纤溶酶原激活剂（tPA）是目前唯一FDA批准的用于治疗急性心肌梗死的药物， 中风，但增加的绝对率的解决症状只有从25%到38%，有必要 另外的治疗方式，以进一步控制或消除脑损伤。我们已经发展了一套 动物脑缺血和出血模型，当以协调的方式使用时， 确定LELI中与其可行性、安全性和有效性相关的许多重要变量， 溶栓治疗。为此，本项目旨在实现以下具体目标：（1） 使用兔小凝块脑栓塞模型（SCEM）检查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 LELI联合tPA在人体中的临床结果。该研究还审查了是否有任何 LELI对大凝块栓塞模型（LCEM）中tPA诱导的脑内血栓形成的影响， 用于警告或安抚临床研究者关于中风患者中LELI副作用的可能性。（二） 开展II期临床试验，检测LELI联合tPA的安全性并初步评估疗效 急性中风患者。 治疗中风的一种方法，除了溶栓，是提供某种形式的神经保护 在中风发作后立即进行，以减少因缺乏血流而造成的损害，并增加 溶栓治疗的机会。第二种策略是在开始给予神经保护后， 血栓溶解以在血栓溶解发生时减少损伤。第三种方法是诱导神经保护， 血栓溶解是完全的，以挽救即使血流已经恢复也会死亡的组织。 最后，制定策略以恢复至少可以恢复某些功能的功能将是有用的。 神经功能LELI有可能产生所有这些效果。的潜在影响 因此，急性中风治疗的研究结果意义深远。

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.