Role of Sleep Disruption after mTBI as a Driver of Chronic Post-traumatic Headache
mTBI 后睡眠中断是慢性创伤后头痛的驱动因素
基本信息
- 批准号:10736602
- 负责人:
- 金额:$ 61.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-01 至 2028-06-30
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAcuteAdrenergic AgentsAdrenergic AntagonistsAdrenergic beta-AntagonistsAgreementBehaviorBiological AssayBlood - brain barrier anatomyBlood VesselsBrainBrain ConcussionCalcitonin Gene-Related PeptideCerebrospinal FluidChronicClinicalClinical TrialsDataDevelopmentElectroencephalographyElectromyographyFaceFilamentGene DeletionHeadacheHumanImpairmentInflammation MediatorsInjuryIntercellular FluidInterventionLightLinkMechanicsMediatingMigraineMusNeuropeptidesPathogenesisPathway interactionsPatientsPeripheralPhotosensitivityPost-Traumatic HeadachesPrazosinPreventionProcessReportingRodentRodent ModelRoleSignal TransductionSleepSleep ArchitectureSleep DeprivationSleep disturbancesSlow-Wave SleepSodium OxybateSupport SystemSymptomsSystemTestingTherapeuticTimeTransgenic MiceVeteransactive dutyallodyniaantagonistaquaporin 4associated symptomawakebehavior measurementbrain dysfunctioncerebrospinal fluid flowcommon symptomdefined contributionexperimental studyfluorescence imagingglymphatic clearanceglymphatic dysfunctionglymphatic functionglymphatic systemimprovedinsightinterstitialmechanical allodyniamild traumatic brain injurymouse modelnoradrenergicnovelnovel strategiespharmacologicpreventservice membersleep behaviorsolutewastingwater channel
项目摘要
PROJECT SUMMARY/ABSTRACT
Migraine-like headaches are among the most frequent complaints following mild traumatic brain injury (mTBI),
yet the mechanisms underlying these headaches are unknown. A possible clue is that sleep disruption is also
a common complaint after mTBI. Sleep disruption is a frequently-reported migraine trigger, while sleep is a
widely effective migraine abortive. Based on the clinical connections between mTBI, headache and sleep
disruption, we hypothesize that sleep disruption contributes to the development of post-traumatic headache
(PTH) following mTBI.
A mechanism that may link mTBI, sleep and PTH is the impairment of the glymphatic system, which is a
recently characterized brain-wide network of perivascular spaces that support the rapid exchange of
cerebrospinal and interstitial fluid. Glymphatic pathway function is greatest during sleep. It is suppressed
during waking by central noradrenergic tone and is reduced by mTBI. We propose that the impairment of
glymphatic function following mTBI may contribute to the development and persistence of PTH symptoms. In
support of this, our preliminary data demonstrate that treatment with the centrally-active α1-adrenergic
antagonist prazosin improves both glymphatic function and ameliorates PTH symptoms in mice. This proposal
will extend these findings by comparing the effects of repetitive impact and blast mTBI on glymphatic function,
testing whether treatment with prazosin can restore post-traumatic glymphatic function. Using well established
mouse models of mTBI and validated behavioral measures of PTH symptoms (light aversion and mechanical
facial allodynia), we will then define the role of glymphatic dysfunction in the development of PTH symptoms by
testing whether these symptoms are exacerbated in a transgenic mouse model in which glymphatic function is
constitutively impaired and whether increasing post-traumatic glymphatic function pharmacologically with
prazosin improves PTH symptoms. In a second set of experiments, we will test whether targeting sleep
provides a pathway for improving post-traumatic glymphatic impairment and ameliorating PTH symptoms. In
these studies we will define whether the effect of sleep augmentation on PTH behaviors is independent of
glymphatic function. In our final studies, we will evaluate whether peripheral or central alpha1 or beta
adrenergic signaling is a key driver of post-traumatic glymphatic impairment, and whether targeting these
processes can improve PTH-associated behaviors either through effect on glymphatic function or through
modulation of post-traumatic sleep.
The results of this study will provide a novel perspective on the mechanisms underlying development of PTH
that will potentially support targeting sleep disruption and glymphatic function as therapeutic strategies for
mTBI patients.
项目摘要/摘要
偏头痛是轻度创伤性脑损伤(MTBI)后最常见的主诉之一,
然而,这些头痛背后的机制尚不清楚。一条可能的线索是,睡眠中断也是
创伤性脑损伤后的常见症状。睡眠障碍是偏头痛的常见诱因,而睡眠是一种
广泛有效的偏头痛流产。基于mTBI、头痛和睡眠之间的临床联系
我们假设睡眠中断会导致创伤后头痛的发生。
(PTH)在mTBI后。
一种可能联系mTBI、睡眠和甲状旁腺激素的机制是淋巴系统的损害,这是一种
最近表征了全脑血管周围空间网络,支持快速交换
脑脊液和间质液体。睡眠期的淋巴通路功能最强。它被抑制了
在清醒时,由中枢去甲肾上腺素能紧张,并被mTBI减少。我们建议,减损
MTBI后的淋巴功能可能有助于PTH症状的发展和持续。在……里面
支持这一点,我们的初步数据表明,用中枢活性的α1-肾上腺素能药物治疗
拮抗剂哌唑嗪既能改善小鼠的淋巴功能,又能改善甲状旁腺素症状。这项建议
将通过比较重复撞击和冲击性mTBI对淋巴功能的影响来扩展这些发现,
检测哌唑嗪治疗能否恢复创伤后淋巴功能。使用成熟的
小鼠mTBI模型和甲状旁腺激素症状的有效行为测量(光厌恶和机械性
面部疼痛),然后我们将通过以下方式确定淋巴功能障碍在甲状旁腺功能障碍症状发展中的作用
在转基因小鼠模型中测试这些症状是否加剧,在转基因小鼠模型中,淋巴功能
体质受损和是否增加创伤后淋巴功能的药理学
哌唑嗪可改善甲状旁腺激素症状。在第二组实验中,我们将测试目标睡眠
为改善创伤后淋巴功能障碍和改善甲状旁腺激素症状提供了途径。在……里面
这些研究我们将确定睡眠增加对甲状旁腺素行为的影响是否独立于
淋巴功能。在我们的最终研究中,我们将评估外周或中枢α1或β1
肾上腺素能信号是创伤后淋巴功能障碍的关键驱动因素,以及是否针对这些
过程可以通过影响淋巴功能或通过
创伤后睡眠的调节。
这一研究结果将为甲状旁腺激素的发病机制提供一个新的视角
这可能会支持将睡眠干扰和淋巴功能作为治疗策略的潜在支持
MTBI患者。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Jeffrey J Iliff其他文献
Jeffrey J Iliff的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Jeffrey J Iliff', 18)}}的其他基金
Tai Chi Practice and Sleep-Active Glymphatic Function
太极拳练习和睡眠活跃类淋巴功能
- 批准号:
10583904 - 财政年份:2023
- 资助金额:
$ 61.15万 - 项目类别:
The role of post-traumatic sleep-wake disruption in the development of tau pathology following mild traumatic brain injury
创伤后睡眠觉醒中断在轻度创伤性脑损伤后 tau 病理学发展中的作用
- 批准号:
10588916 - 财政年份:2023
- 资助金额:
$ 61.15万 - 项目类别:
Defining the role of age-related glymphatic pathway impairment in amyloid beta plaque deposition
定义年龄相关的类淋巴通路损伤在淀粉样β斑块沉积中的作用
- 批准号:
10198706 - 财政年份:2017
- 资助金额:
$ 61.15万 - 项目类别:
Defining the role of age-related glymphatic pathway impairment in amyloid beta plaque deposition
定义年龄相关的类淋巴通路损伤在淀粉样β斑块沉积中的作用
- 批准号:
10003575 - 财政年份:2017
- 资助金额:
$ 61.15万 - 项目类别:
Defining the role of age-related glymphatic pathway impairment in amyloid beta plaque deposition
定义年龄相关的类淋巴通路损伤在淀粉样β斑块沉积中的作用
- 批准号:
9214181 - 财政年份:2017
- 资助金额:
$ 61.15万 - 项目类别:
Role of perivascular aquaporin-4 polarization in post-traumatic neurodegeneration
血管周围水通道蛋白 4 极化在创伤后神经变性中的作用
- 批准号:
9309096 - 财政年份:2015
- 资助金额:
$ 61.15万 - 项目类别:
相似海外基金
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
- 批准号:
MR/X02329X/1 - 财政年份:2024
- 资助金额:
$ 61.15万 - 项目类别:
Fellowship
Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
- 批准号:
MR/Y009568/1 - 财政年份:2024
- 资助金额:
$ 61.15万 - 项目类别:
Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
- 批准号:
10090332 - 财政年份:2024
- 资助金额:
$ 61.15万 - 项目类别:
Collaborative R&D
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
- 批准号:
MR/X021882/1 - 财政年份:2024
- 资助金额:
$ 61.15万 - 项目类别:
Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
- 批准号:
2312694 - 财政年份:2024
- 资助金额:
$ 61.15万 - 项目类别:
Standard Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
- 批准号:
EP/Y003527/1 - 财政年份:2024
- 资助金额:
$ 61.15万 - 项目类别:
Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
- 批准号:
EP/Y030338/1 - 财政年份:2024
- 资助金额:
$ 61.15万 - 项目类别:
Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
- 批准号:
MR/X029557/1 - 财政年份:2024
- 资助金额:
$ 61.15万 - 项目类别:
Research Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
- 批准号:
24K19395 - 财政年份:2024
- 资助金额:
$ 61.15万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Collaborative Research: Changes and Impact of Right Ventricle Viscoelasticity Under Acute Stress and Chronic Pulmonary Hypertension
合作研究:急性应激和慢性肺动脉高压下右心室粘弹性的变化和影响
- 批准号:
2244994 - 财政年份:2023
- 资助金额:
$ 61.15万 - 项目类别:
Standard Grant