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

血脑屏障和偏头痛：对治疗的影响（多样性补充）

基本信息

批准号：
10404773
负责人：
Tally Marie Milnes
金额：
$ 3.23万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-29 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10404773
关键词：
Address Affect American Analytical Chemistry Animals Behavioral Bioinformatics Biological Biological Assay Blood Blood - brain barrier anatomy Brain Cell Culture Techniques Chronic disabling pain Clinical Communities Data Disease Drug Delivery Systems Endothelial Cells Endothelium Enzyme-Linked Immunosorbent Assay Estrogen Receptor beta Female Future Genetic Goals Gonadal Steroid Hormones Headache Headache Disorders High Pressure Liquid Chromatography Homeostasis Hormones In Situ In Vitro Inflammatory Investigation Knowledge Learning Light Measures Mediating Methods Migraine Modality Molecular Movement NHE1 Nervous system structure Neuropeptides Nociception Outcome Measure Pain Pain intensity Paper Pathology Pathway Analysis Patients Pattern Perfusion Periodicity Permeability Pharmaceutical Preparations Pharmacology Pharmacotherapy Physiological Population Prevalence Prevention Process Production Publishing Recurrence Regulation Reporting Research Research Personnel Risk Role Schools Sensory Sex Differences Stroke Sumatriptan Symptoms Techniques Testing Therapeutic Therapeutic Studies Time Training Treatment Efficacy Trigeminal System Western Blotting Woman Work Writing Xenobiotics animal tissue bioinformatics network blood-brain barrier disruption brain endothelial cell brain parenchyma career central sensitization chronic pain cutaneous allodynia disability experience experimental study female sex hormone functional loss graduate student hormone regulation immunocytochemistry in vivo in vivo evaluation interest laboratory experience male men monolayer nervous system disorder neurovascular pain outcome pain perception parent grant prophylactic relating to nervous system sensory input sensory stimulus sex sound transgender uptake

项目摘要

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.

项目概要偏头痛是一种原发性头痛疾病，女性与男性的发病比例为 3:1，其特点是由三叉神经系统的中枢敏化引起的慢性疼痛发作的周期性模式和各种其他神经血管机制会产生一种疼痛感知强烈增强的疾病状态。偏头痛通常是由环境感觉刺激引发的，例如光和声音，其中平庸的感觉刺激大量的感觉输入变得有害并引起头痛，这表明适应不良的关联伤害感受和感觉处理网络之间的差异可能是根本原因。神经损伤导致改变功能连接，增加炎症神经肽的产生；和功能失调的特定模态的感觉信息的整合和处理被认为是偏头痛。这些都与血脑屏障稳态的破坏有关。完整性降低 BBB 可以增加或减少疾病期间进入大脑的异生物质的量研究偏头痛期间不同性别的治疗效果有何不同的合理性。该提案将确定男性和女性之间抗偏头痛血液到大脑的摄取是否因生理原因而存在差异通过测试NHE1的性激素调节通过的假设来观察血脑屏障的差异脑内皮细胞中的 ERbeta 以性别依赖性方式调节舒马曲坦从血液到大脑的摄取。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

DAGLα Inhibition as a Non-invasive and Translational Model of Episodic Headache.

DOI：
10.3389/fphar.2020.615028
发表时间：
2020
期刊：
Frontiers in pharmacology
影响因子：
5.6
作者：
Levine A;Liktor-Busa E;Karlage KL;Giancotti L;Salvemini D;Vanderah TW;Largent-Milnes TM
通讯作者：
Largent-Milnes TM

Inhibition of HSP90 Preserves Blood-Brain Barrier Integrity after Cortical Spreading Depression.

DOI：
10.3390/pharmaceutics14081665
发表时间：
2022-08-10
期刊：
PHARMACEUTICS
影响因子：
5.4
作者：
Palomino, Seph M.;Levine, Aidan A.;Wahl, Jared;Liktor-Busa, Erika;Streicher, John M.;Largent-Milnes, Tally M.
通讯作者：
Largent-Milnes, Tally M.

Sex hormones regulate NHE1 functional expression and brain endothelial proteome to control paracellular integrity of the blood endothelial barrier.

DOI：
10.1016/j.brainres.2021.147448
发表时间：
2021-07-15
期刊：
Brain research
影响因子：
2.9
作者：
通讯作者：

Extracellular Alterations in pH and K+ Modify the Murine Brain Endothelial Cell Total and Phospho-Proteome.

DOI：
10.3390/pharmaceutics14071469
发表时间：
2022-07-15
期刊：
PHARMACEUTICS
影响因子：
5.4
作者：
Wahl, Jared R.;Vivek, Anjali;Palomino, Seph M.;Almuslim, Moyad;Cottier, Karissa E.;Langlais, Paul R.;Streicher, John M.;Vanderah, Todd W.;Liktor-Busa, Erika;Largent-Milnes, Tally M.
通讯作者：
Largent-Milnes, Tally M.

Molecular mechanisms of hormones implicated in migraine and the translational implication for transgender patients.