Brain K+ Dynamics, BBB Breakdown & Hemorrhagic Transformation in Ischemic Stroke

多模式CT和MRI可用于研究和诊断中风的病理进展，可排除 出血性中风，可能可以用来延长溶栓时限，但没有办法 确定溶栓后再通增加卒中后发生率的时限 出血性转化(HT)。利用实验性缺血，我们提出了一种估计指标的方法。 明确溶栓时限。这种方法将提供一条关键的信息，而不是- 目前可用的：在没有出血性中风的情况下，预测溶栓是否会导致 太好了。我们的假设是，当服用溶栓剂后，HT的发生频率会增加。 血脑屏障(BBB)的最初破坏。这项建议的理由是基于我们的观察者- 阻断后3~4h，缺血区皮层脑组织钾离子[K+]br突然下降75%。我们 建议[K+]br的这种突然下降，即“K+下降”，预示着血脑屏障崩溃的开始，甚至- 实际上导致再灌流后的心肌梗死。我们将使用K/Rb替代磁共振来观察这一[K+]下降。Rb-87， 但不是K，可以通过MRI有效地观察到，作为K+的同系物，可以替代K (18%)通过喂食。我们将使用Rb MRI在大鼠大脑中对[K+]br的这种下降进行计时，并将研究其关系 三种不同再灌流缺血模型(包括含tPA的栓子模型)中羟色胺的发生率 在不同时间给药以及在再灌流后添加tPA的机械模型)，作为 中风的模型和严重程度，以及不同的侧支血流潜力。我们预测这种情况会增加。 当再灌流发生在[K*]下降之后而不是在此之前，且血脑屏障通透性改变将 与K+下降相吻合。此外，我们将评估这种[K+]br下降与其他MRI参数(T1、 T2、ADC、AST CBF、[Na+]br)，并预测它将发生在特定水平的[Na+]br 除Gd-DTPA外渗外渗与其他参数无关。这些结果将合并在一起 用放射自显影CBF和组织分析测定K、Rb和Na。间接因素(包括温度和 血清电解质)将被用来改变K+下降的时间：假设随后会发生血脑屏障改变 西装。这项建议对血脑屏障破裂与高血压的关系的调查可能直接导致额外的死亡。 急性缺血性卒中的评估和治疗方面的未知和治疗进展。

Multimodal CT and MRI are available to study and diagnose stroke pathological progression, can rule out hemorrhagic stroke, and possibly can be used to extend the time limit for thrombolysis, but there is no way to determine the time limit after which reperfusion with thrombolysis increases the occurrence of post-stroke hemorrhagic transformation (HT).Using experimental ischemia, we propose a method to estimate the indi- vidual time limit for thrombolysis. This method would provide a crucial piece of information that is notcur- rently available: the ability to predict whether thrombolysis, in the absence of hemorrhagic stroke, will cause HT. Our hypothesis is that the frequency of HT will increase when a thrombolytic agent is administered after the initial breakdown of the blood-brain barrier (BBB). The rationale for this proposal is based on our obser- vation of a sudden fall of 75% in brain tissue potassium, [K+]br, in ischemic cortex 3-4 h after occlusion. We propose that this abrupt decrease in [K+]br, the "K+ drop," indicates the start of BBB breakdown, which even- tually leads to HT after reperfusion. We will use K/Rb substitution MRI to observe this [K+]brfall. Rubidium-87, but not K, can be effectively observed with MRI,acts as a congener of K+, and can be substituted for K (18%) by feeding. We will time this drop in [K+]br using Rb MRI in the rat brain, and will investigate its relation to the frequency of HT in three different reperfusion ischemic models (including an embolus model with tPA administered at various times and a mechanical model with added tPA after reperfusion), as a function of stroke model and severity, and varying collateral blood flow potential. We predict the increased occurrence of HT when reperfusion occurs after, but not before, this fall in [K*]^, and that BBB permeability changes will coincide with the K+ drop. In addition, we will assess this [K+]br drop in relation to other MRI parameters(T1, T2, ADC, AST CBF, [Na+]br) in the ischemic core and predict that it will occur at a specific level of [Na+]br but will not be related to any other parameter except for Gd-DTPA extravasation. These results will be combined with autoradiographic CBF and tissue analysis for K, Rb, and Na. Indirect factors (including temperature and serum electrolytes) will be used to change the time of the K+ drop: BBB changes are hypothesized to follow suit. This proposal's investigation of the relation of BBB breakdown to HT could lead directly to additional di- agnostic and therapeutic advances in the assessment and management of acute ischemic stroke.