Developing antibodies to diagnose cerebral vasospasm

描述(由申请人提供) 我们还没有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。这些分解产品是由 通过胆红素的氧化，我们称之为胆红素氧化产物： 盒子。因为它们在体外和体内都会引起血管痉挛，而在 对于非脑血管痉挛患者的脑脊液，我们认为盒的浓度 将是一个客观和定量的脑部预测(或评估)指标 蛛网膜下腔出血患者的血管痉挛。因此，我们将针对这些盒子制造抗体 并使用这些新抗体通过以下方式诊断和/或预测脑血管痉挛 检测SAH患者脑脊液中它们的含量。 在动脉瘤破裂引起的蛛网膜下腔出血后，AS 多达40%的幸存患者会出现脑血管痉挛。很多病人 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。所需要的是一种具体、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 预测或评估蛛网膜下腔出血(SAH)所致的脑 血管痉挛。诊断通常取决于临床参数，如 作为局灶性神经症状和/或血管造影明显的血管痉挛，这 诊断通常是在出现血管痉挛和中风后做出的。 我们已经在SAH患者的脑脊液中发现了新的分子 通过对胆红素的氧化，表明盒子(但不是纯胆红素 单独)在体外和体内引起血管痉挛。这让我们得出了这样的假设： 会导致蛛网膜下腔出血后脑血管痉挛 这些化合物的存在和/或浓度将预测和关联 伴随着血管痉挛的发生。 在这个项目中，我们将制作针对我们的三个盒子的多克隆抗体 已经识别并确定了这些抗体检测盒子的能力 在；1)对照溶液中，2)在脑脊液中添加已知浓度的BOX，3) 来自不使用BOX的血管痉挛患者的脑脊液，以及4)与 脑脊液中BOX浓度与脑血管痉挛临床参数的关系。这些数据将 提供针对BOX的抗体可用于诊断的概念证明 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.