Serum markers of brain barriers

描述（由申请人提供）：血脑屏障（BBB）保护大脑免受全身影响，并积极参与中枢神经系统稳态的控制。BBB功能丧失在多种神经系统疾病中很常见。取决于所涉及的神经学病症并且鉴于BBB还阻止有用的化疗剂进入的事实，BBB开口可能是有利的和有害的。BBB衰竭的确切时间过程及其对疾病进展的病因学贡献知之甚少，主要是因为没有可靠的外周标志物，并且BBB的黄金放射学标准尚未确定。发现BBB功能的成像策略或替代标记物被确定为该计划公告的首要任务。我们的初步结果表明，特定脑或CSF蛋白（如S100 P）的外周测量是可重复的，侵入性较小，成本较低的替代对比CT/MRI或CSF采样确定BBB的完整性。一个替代的，容易获得的，非放射学标记受损的血脑屏障功能可能是在识别患者的各种神经系统疾病，包括转移性脑肿瘤，神经胶质瘤，中风，多发性硬化症，头部损伤等，我们开发了一个多步骤的例行允许血脑屏障开放之前和之后的血浆蛋白检测的显着价值。许多问题仍然没有答案。S100 P是唯一有用的外周血血脑屏障功能标志物吗？标记物积累的时间过程是什么？推测的标记物如何与被认为与BBB渗漏相关的不同MRI/CT模式相关？我们将使用分子和蛋白质检测技术，以发现新的标志物的血脑屏障的完整性或泄漏，并测试的假设，即增加的血浆与脑脊液的比例S100 P或其他血脑屏障标志物相关的时间和定性与血脑屏障损伤的放射性措施。最后，我们将验证这些标记物在早期检测复发性脑肿瘤或转移中的有用性，以明确说明PA的任务之一。

DESCRIPTION (provided by applicant): The blood-brain barrier (BBB) shields the brain from systemic influences, and actively participates to the control of central nervous system homeostasis. Loss of BBB function is common in a variety of neurological disorders. Depending on the neurological condition involved and given the fact that the BBB also prevents entry of useful chemotherapeutic agents, BBB openings may be both advantageous and damaging. The exact time course of BBB failure, and its etiological contribution to disease progression is poorly understood mainly because reliable peripheral markers are not available and since golden radiologic standards of BBB are yet to be determined. The discovery of imaging strategies or surrogate markers of BBB function were identified a top priority for this Program announcement. Our preliminary results suggest that peripheral measurements of specific brain or CSF proteins (e.g. S100P) are reproducible, less invasive and less costly alternative to contrast CT/MRI or CSF sampling for determining BBB integrity. A surrogate, readily available, non-radiologic marker for impaired BBB function may be of significant value in identifying patients with a variety of neurological disorders, including metastatic brain tumors, gliomas, stroke, multiple sclerosis, head injury, etc. We developed a multi-step routine that allows detection of plasma proteins prior to and after BBB opening. Many questions remain unanswered. Is S100P the only useful peripheral marker of BBB function? What is the time course of the marker's accumulation? How do putative markers correlated with different MRI/CT patterns believed to be associated with BBB leakage? We will use molecular and protein-detection techniques to discover new markers of BBB intactness or leakage and to test the hypothesis that an increased plasma-to CSF ratio of S100P or other BBB markers correlates temporally and qualitatively with radiological measures of BBB impairment. Finally, we will validate the usefulness of these markers in the early detection of recurrent brain tumors or metastases, to specifically address one of the mandates of this PA.