Blood Brain Barrier and Migraine: Effect on Therapy (Diversity Supplement)

项目摘要 偏头痛是一种主要的头痛疾病，女性与男性的比例为3：1，偏头痛的特征是 三叉神经中枢敏感化引起的慢性疼痛发作的周期性模式 各种其他神经血管机制，以创造一种疾病状态，在这种状态下，痛觉强烈增强。 偏头痛通常是由环境感官刺激引发的，如光和声音，其中平庸的 大量的感觉输入变得有害并导致头痛，这表明适应不良联系 伤害性感觉和感觉处理网络之间的关系可能是潜在的原因。神经损伤先导 改变功能连接，增加炎性神经肽的产生；以及功能障碍 通道特有的感觉信息的整合和处理被认为是 偏头痛。其中每一种都与血脑屏障动态平衡的破坏有关。完整性降低 血脑屏障可以增加或减少疾病提供期间进入大脑的外来物质的数量。 这是研究偏头痛期间不同性别之间治疗效果差异的合理方法。这项提议将 确定男性和女性对抗偏头痛血液到大脑的摄取是否因生理原因而不同 通过检验NHE1通过性激素调节的假说，血脑屏障的差异 脑内皮细胞中的ERbeta以性别依赖的方式调节舒马曲坦的血到脑的摄取。

Project Summary Migraine is a primary headache disorder that affects women at a 3:1 ratio as compared to men which features a cyclical pattern of chronic pain attacks resulting from central sensitization of the trigeminal nervous system and various other neurovascular mechanisms to create a disease state wherein pain perception is intensely heightened. Migraine headaches are often triggered by environmental sensory stimuli, such as light and sound, wherein banal amounts of sensory input become noxious and induce headache suggesting that maladaptive association between the nociceptive and sensory processing networks could be the underlying cause. Neural damage leading to altered functional connectivity, increased production of inflammatory neuropeptides; and dysfunctional integration and processing of modality-specific sensory information are thought to be some mechanisms of migraine. Each of these is also implicated disruption of blood brain barrier homeostasis. Decreased integrity of the BBB can either increase or decrease the amount of xenobiotics entering the brain during disease providing a rational to study how therapeutic efficacy varies between the sexes during migraine. This proposal will determine if antimigraine blood to brain uptake differs between male and females because of physiological differences in the blood brain barrier by testing the hypothesis that sex hormone regulation of NHE1 through ERbeta in brain endothelial cells regulates sumatriptan blood-to-brain uptake in a sex dependent manner.