Developing antibodies to diagnose cerebral vasospasm

描述（由申请人提供） 我们发现，胆红素分解产物存在于脑脊液中， 蛛网膜下腔出血（SAH）患者。这些分解产物产生于 通过胆红素的氧化，我们称这些胆红素氧化产物为： 箱.因为它们在体外和体内都会引起血管痉挛，而在 在非血管痉挛患者的CSF中，我们认为BOXes的浓度 将是一个客观和定量的预测（或评估）大脑 SAH患者的血管痉挛。因此，我们将制造针对BOX的抗体 并使用这些新的抗体来诊断和/或预测脑血管痉挛， 在SAH患者的CSF中检测它们。 动脉瘤破裂引起蛛网膜下腔出血后，如 多达40%的存活患者发生脑血管痉挛。许多患者 被诊断为脑血管痉挛，但通常只有在他们 患上了无法治愈的中风我们需要的是一个具体、快速和简单的 预测血管痉挛的方法。目前还没有具体的测试方法， 预测或评估蛛网膜下腔出血（SAH）引起的脑出血 血管痉挛诊断通常取决于临床参数， 作为局灶性神经系统体征和/或血管造影明显的血管痉挛， 诊断通常是在出现血管痉挛和中风后作出的。 我们已经在SAH患者的CSF中发现了新的分子， 通过胆红素的氧化，并表明BOX（但不是纯胆红素） 单独）在体外和体内引起血管痉挛。这让我们假设： BOXs引起蛛网膜下腔出血后的脑血管痉挛， 这些化合物存在和/或浓度将预测和关联 与血管痉挛的发生有关。 在这个项目中，我们将针对三个盒子， 已经鉴定并确定了这些抗体检测BOX的能力 在：1）对照溶液，2）加标已知浓度BOX的CSF，3） 来自血管痉挛患者的CSF，而不加BOXes，以及4）将 CSF中的BOX浓度与血管痉挛的临床参数。这些数据将 提供概念证明，抗BOXes抗体可用于诊断 并预测SAH患者的血管痉挛。

DESCRIPTION (provided by applicant) We nave discovered that bilirubin breakdown products are present in the CSF of subarachnoid hemorrhage (SAH) patients. These breakdown products are produced by the oxidation of bilirubin and we call these Bilirubin OXidation products: BOXes. Because they cause vasospasm in vitro and in vivo, and are not found in the CSF of nonvasospasm patients, we believe that the concentration of BOXes will be an objective and quantitative predictor (or assessor) of cerebral vasospasm in SAH patients. Therefore, we will make antibodies against the BOXes and use these new antibodies to diagnose and/or predict cerebral vasospasm by detecting them in the CSF of SAH patients. Following a subarachnoid hemorrhage caused by the rupture of an aneurysm, as many as 40% of the surviving patients develop cerebral vasospasm. Many patients are diagnosed with cerebral vasospasm, but frequently only after they have developed an untreatable stroke. What is needed is a specific, quick and easy method for predicting vasospasm. Currently, there is no specific test for predicting or assessing subarachnoid hemorrhage (SAH) induced cerebral vasospasm. The diagnosis is generally dependent upon clinical parameters such as focal neurological signs and/or angiographically evident vasospasm, and this diagnosis is usually made after there is vasospasm and stroke. We have identified novel molecules in the CSF of SAH patients that are produced by the oxidation of bilirubin and shown that the BOXes (but not pure bilirubin alone) cause vasospasm in vitro and in vivo. This has led us to hypothesize: that BOXes cause cerebral vasospasm following subarachnoid hemorrhage and that the presence and/or concentration of these compounds will predict and correlate with the occurrence of vasospasm. In this project we will make polyclonal antibodies against the three BOXes we have identified and determine the ability of these antibodies to detect BOXes in; 1) control solutions, 2) CSF spiked with known concentrations of BOXes, 3) CSF from vasospasm patients without spiking with BOXes, and 4) correlate the BOX concentrations in CSF to clinical parameters of vasospasm. These data will provide proof of concept that antibodies against BOXes can be used to diagnose and predict vasospasm in SAH patients.