Clinical and molecular pathophysiology of headache

头痛的临床和分子病理生理学

• 批准号: 6998872
• 负责人: Michael Gordon Harrington
• 金额: $ 34.58万
• 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/6998872
• 关键词: Clinical; molecular; pathophysiology; headache

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、期间和之后发生的临床和分子变化。我们的假设是，无数的头痛触发因素和行为表达是通过相互作用的分子途径介导的，这些途径可以通过对可接触的体液，特别是脑脊液（CSF）进行时间、成分分析来研究。初步结果揭示了蛋白质、脂质和元素的许多发作变化，这些变化反映了这些偏头痛“门户”途径，其程度反映了偏头痛发作的临床严重程度，表明存在相应的“分子发作”。我们建议通过分析头痛和非头痛状态的偏头痛患者、阵发性紧张性头痛患者和不头痛的“对照”的脑脊液，进一步剖析这种临床和分子发作。我们将通过 2D 凝胶电泳、液相色谱和质谱法对临床上明确定义的参与者的时间间隔集合来确定蛋白质、脂质和元素变化的分子组成，从而测试蛋白质、脂质和元素变化在头痛中的作用。对这些成分差异的描述应该将我们的病理生理学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补救措施或干预措施。

项目成果

Na,K-ATPase alpha isoforms at the blood-cerebrospinal fluid-trigeminal nerve and blood-retina interfaces in the rat.

• DOI: 10.1186/2045-8118-10-14
• 发表时间: 2013-03-14
• 期刊: Fluids and barriers of the CNS
• 影响因子: 7.3
• 作者: Arakaki X;McCleary P;Techy M;Chiang J;Kuo L;Fonteh AN;Armstrong B;Levy D;Harrington MG
• 通讯作者: Harrington MG

Altered brainstem auditory evoked potentials in a rat central sensitization model are similar to those in migraine.

• DOI: 10.1016/j.brainres.2014.03.033
• 发表时间: 2014-05-14
• 期刊: BRAIN RESEARCH
• 影响因子: 2.9
• 作者: Arakaki, Xianghong;Galbraith, Gary;Pikov, Victor;Fonteh, Alfred N.;Harrington, Michael G.
• 通讯作者: Harrington, Michael G.

Phospholipase C activity increases in cerebrospinal fluid from migraineurs in proportion to the number of comorbid conditions: a case-control study.

偏头痛患者脑脊液中磷脂酶 C 活性的增加与合并症的数量成正比：一项病例对照研究。

• DOI: 10.1186/1129-2377-14-60
• 发表时间: 2013
• 期刊: The journal of headache and pain
• 作者: Fonteh,AlfredN;Pogoda,JaniceM;Chung,Rainbow;Cowan,RobertP;Harrington,MichaelG
• 通讯作者: Harrington,MichaelG

Cerebrospinal fluid sodium rhythms.

• DOI: 10.1186/1743-8454-7-3
• 发表时间: 2010-01-20
• 期刊: Cerebrospinal fluid research
• 作者: Harrington MG;Salomon RM;Pogoda JM;Oborina E;Okey N;Johnson B;Schmidt D;Fonteh AN;Dalleska NF
• 通讯作者: Dalleska NF

The morphology and biochemistry of nanostructures provide evidence for synthesis and signaling functions in human cerebrospinal fluid.

• DOI: 10.1186/1743-8454-6-10
• 发表时间: 2009-09-07
• 期刊: Cerebrospinal fluid research
• 作者: Harrington MG;Fonteh AN;Oborina E;Liao P;Cowan RP;McComb G;Chavez JN;Rush J;Biringer RG;Hühmer AF
• 通讯作者: Hühmer AF