Clinical and molecular pathophysiology of headache

头痛的临床和分子病理生理学

• 批准号: 6573651
• 负责人: Michael Gordon Harrington
• 金额: $ 35.41万
• 依托单位: HUNTINGTON MEDICAL RESEARCH INSTITUTES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6573651
• 关键词: biomarker; cerebrospinal fluid; clinical research; enzyme linked immunosorbent assay; high performance liquid chromatography; human subject; lipids; liquid chromatography mass spectrometry; migraine; molecular pathology; proteins; two dimensional gel electrophoresis

DESCRIPTION (provided by applicant): The long-term objective of our research is to discover what clinical and molecular changes occur before, during and after severe headaches. Our hypothesis is that the myriad headache triggers and behavioral expressions are mediated through interacting molecular pathways that may be studied by temporal, compositional analysis of accessible body fluids, in particular cerebrospinal fluid (CSF). Preliminary results have revealed many ictal changes in proteins, lipids and elements that reflect these migraine 'gateway' pathways, the magnitude of which reflect the clinical severity of the migraine ictus, suggesting a corresponding 'molecular ictus'. We propose to further dissect this clinical and molecular ictus by the analysis of CSF from migraineurs in headache and non-headache states, episodic tension headache sufferers and 'controls' who do not suffer from headaches. We will test the role of protein, lipid and elemental changes in headache by defining their molecular composition by 2D gel electrophoresis, liquid chromatography and mass spectrometry in temporally spaced collections from clinically well defined participants. Delineation of these compositional differences should extend our pathophysiological understanding beyond the current theories, yield useful biomarkers and lead to more knowledge-based remedies or interventions.

描述（由申请人提供）：我们研究的长期目标是发现严重头痛之前，之中和之后发生的临床和分子变化。我们的假设是，无数的头痛触发和行为表达是通过相互作用的分子途径来介导的，分子途径可以通过时间分析，可访问的身体流体，特别是脑脊液（CSF）来研究。初步结果揭示了反映了这些偏头痛的“网关”途径的蛋白质，脂质和元素的许多发射变化，其大小反映了偏头痛ICTUS的临床严重程度，表明了相应的“分子ICTUS”。我们建议通过在头痛和非头痛状态中对CSF的分析，不遭受头痛的偏头痛，情节张力头痛患者和“控制”，进一步剖析了这种临床和分子ICTU。我们将通过2D凝胶电泳，液相色谱和质谱法在临床上定义良好的参与者的时间间隔集合中定义其分子组成，通过定义其分子组成，测试蛋白质，脂质和元素变化的作用。这些组成差异的描述应将我们的病理生理理解扩展到当前理论之外，产生有用的生物标志物并导致更多基于知识的疗法或干预措施。