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

项目摘要 偏头痛是一种原发性头痛疾病，与男性相比，女性的比例为3：1，其特征是 三叉神经系统中枢致敏导致的慢性疼痛发作的周期性模式， 各种其他神经血管机制，以产生其中疼痛感知强烈增强的疾病状态。 偏头痛通常由环境感官刺激引发，例如光和声音，其中平庸的 大量的感觉输入变得有害并引起头痛，这表明适应不良的联想 可能是潜在的原因神经损伤导致 改变功能连接，增加炎症神经肽的产生;和功能障碍 特定感觉信息的整合和加工被认为是 偏头痛这些中的每一个也涉及血脑屏障稳态的破坏。完整性降低 血脑屏障可以增加或减少在疾病提供期间进入脑的外源性物质的量， 研究偏头痛的治疗效果在性别之间的差异是合理的。这项建议会 确定抗偏头痛药物的血脑摄取是否因生理因素而在男性和女性之间存在差异。 血脑屏障的差异，通过测试性激素调节NHE 1的假设， 脑内皮细胞中的ER β以性别依赖性方式调节舒马曲坦的血脑摄取。

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.