Miniscope in vivo imaging of cumulative traumatic brain injury
累积性脑外伤的微型活体成像
基本信息
- 批准号:10841846
- 负责人:
- 金额:$ 4.49万
- 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 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAcuteAnesthesia proceduresAnxietyAutomobile DrivingBehaviorBehavioralBlood flowBlurred visionBrainCephalicCerebrovascular CirculationClinical ManagementClinical ResearchClosed head injuriesCognitiveDataDextransDisinhibitionDizzinessDropsDrowsinessEmotionalExtravasationFemaleFluorescenceFunctional disorderFutureHeadHeadacheHealth Care CostsHelmetHyperalgesiaImageImpairmentIndividualInjuryInvestigationLocationMechanicsMemoryMental DepressionMicroscopeMicroscopyMonitorMusNervous System PhysiologyNeurologicNeurologic DysfunctionsNeurological outcomePainPatientsPerformancePersonsPhysiologicalPost-Concussion SyndromeRecoveryReportingSleepSleep DisordersSleeplessnessSymptomsTestingTimeTraumatic Brain InjuryUnited StatesVisualizationWeightblood-brain barrier permeabilizationcare costsexecutive functionhead impactimaging modalityin vivoin vivo imaginginsightintraperitonealmalemild traumatic brain injuryminiaturizeneurobehavioralneurophysiologynovelresponserestraintsocietal costssomatosensoryspatial memory
项目摘要
Project Summary/Abstract
In the United States, millions of people sustain a traumatic brain injury (TBI) each year carrying individual,
healthcare, and societal costs greater than $45 billion annually. Mild TBI (mTBI) accounts for more than 75% of
all TBIs, with many individuals sustaining more than one. mTBI patients report post-concussion syndrome (PCS)
symptoms that include sleep disorders (insomnia, daytime sleepiness), somatic symptoms (dizziness, headache,
blurred vision), cognitive complaints (memory, executive function), and emotional problems (anxiety, depression,
irritability, disinhibition). For many, PCS is transient, and still 10-25% report persistent PCS symptoms. The
enigmatic PCS symptom presentation and persistence after mTBI urges investigation into dynamic responses
in the brain that tie acute neurophysiology to behavioral function. The investigative team has refined in vivo
imaging methods of miniaturized microscopes (miniscopes) to evaluate cerebral blood flow (CBF) and blood
brain barrier (BBB) permeability in the unrestrained, behaving mouse. New preliminary data leverage the
miniscope headcap to induce impact acceleration (weight drop) closed head injury. The data driving this proposal
show immediate accumulation of fluorescent dextrans in the parenchyma within the field of view. The strength
of this approach eliminates anesthesia during long-duration imaging, permits naturalistic behavior without head
restraint, and locks into a baseplate for repeated imaging of single channel, wide-field, fluorescence. For the first
time, the cumulative effects of TBI on neurophysiology (CBF, BBB permeability, sleep) can be regressed toward
neurobehavioral impairments. The present proposal tests the hypothesis that the cumulative effects of
mTBI on CBF and BBB permeability promote post-traumatic sleep and predict neurological impairments.
Male and female mice are prepared for miniscope imaging through a cranial window and attached baseplate.
The baseplate headcap substitutes for a helmet in closed-head impact acceleration TBI. With a 15 sec transition,
miniscopes visualize CBF and BBB permeability with intraperitoneal dextrans (40-2000 kDa) in vasculature and
parenchyma, respectively. The cumulative effects of mTBI are assessed with impacts delivered twice daily, daily,
or every other day for a week. Aim 1 monitors the cumulative effects of mTBI with varying temporal spacing on
CBF concurrent with post-traumatic sleep and subacute behavioral performance. Aim 2 quantifies the extent of
dextran extravasation with post-traumatic sleep and subacute neurological performance. Neurological outcomes
include anxiety (open field), spatial memory (novel object location), and somatosensory pain (mechanical
hyperalgesia). Twice daily injuries likely show temporal summation of CBF, BBB permeability, and sleep effects,
which are recovered with longer recovery times between injuries. The integration of miniscope imaging and
closed head injury can propel future studies on physiological perturbations and clinical management of TBI.
项目总结/摘要
在美国,每年有数百万人遭受创伤性脑损伤(TBI),
医疗保健和社会成本每年超过450亿美元。轻度TBI(mTBI)占75%以上,
所有TBI,许多人持续一个以上。mTBI患者报告脑震荡后综合征(PCS)
包括睡眠障碍(失眠,白天嗜睡),躯体症状(头晕,头痛,
视力模糊),认知问题(记忆,执行功能),和情绪问题(焦虑,抑郁,
易激惹、抑制解除)。对于许多人来说,PCS是短暂的,仍然有10-25%的人报告持续的PCS症状。的
mTBI后神秘的PCS症状表现和持续性促使研究动态反应
将急性神经生理学与行为功能联系起来。调查小组在体内提炼了
评价脑血流量(CBF)和血液的微型显微镜(微型镜)成像方法
脑屏障(BBB)的通透性在不受限制的,行为小鼠。新的初步数据利用了
微型摄像头头帽导致撞击加速度(重量下降)闭合性头部损伤。推动这一提议的数据
显示荧光葡聚糖在视野内的实质中立即积聚。强度
这种方法消除了长时间成像过程中的麻醉,
限制,并锁定到基板上,用于单通道、宽视野、荧光的重复成像。第一
随着时间的推移,TBI对神经生理学(CBF,BBB渗透性,睡眠)的累积影响可以回归到
神经行为障碍本提案检验的假设是,
mTBI对CBF和BBB渗透性的影响促进创伤后睡眠并预测神经损伤。
准备雄性和雌性小鼠用于通过颅窗和附接的基板进行微型镜成像。
底板头帽在闭头冲击加速度TBI中代替头盔。15秒的过渡,
微型内窥镜用腹膜内葡聚糖(40-2000 kDa)在血管系统中显示CBF和BBB渗透性,
薄壁组织。mTBI的累积效应通过每天两次、每天
或者一周内每隔一天目标1监测不同时间间隔的mTBI对
脑血流与创伤后睡眠和亚急性行为表现的关系目标2量化了
葡聚糖外渗与创伤后睡眠和亚急性神经功能表现。神经功能结局
包括焦虑(旷场)、空间记忆(新物体位置)和躯体感觉疼痛(机械性
痛觉过敏)。每天两次损伤可能显示CBF、BBB渗透性和睡眠效应的时间总和,
在两次受伤之间的恢复时间较长。微型显微镜成像与
闭合性颅脑损伤可以推动未来对TBI的生理扰动和临床管理的研究。
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 }}
JONATHAN LIFSHITZ其他文献
JONATHAN LIFSHITZ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('JONATHAN LIFSHITZ', 18)}}的其他基金
Molecular Tool Development to Identify, Isolate, and Interrogate the Rod Microglia Phenotype in Neurological Disease and Injury
开发分子工具来识别、分离和询问神经系统疾病和损伤中的杆状小胶质细胞表型
- 批准号:
10599762 - 财政年份:2023
- 资助金额:
$ 4.49万 - 项目类别:
Miniscope in vivo imaging of cumulative traumatic brain injury
累积性脑外伤的微型活体成像
- 批准号:
10648962 - 财政年份:2023
- 资助金额:
$ 4.49万 - 项目类别:
Gravida traumatic brain injury (TBI) impacts neurodevelopment of the offspring
妊娠创伤性脑损伤(TBI)影响后代的神经发育
- 批准号:
10734284 - 财政年份:2023
- 资助金额:
$ 4.49万 - 项目类别:
Mechanistic role of vascular dysfunction in TBI-mediated cognitive dysfunction
血管功能障碍在 TBI 介导的认知功能障碍中的机制作用
- 批准号:
10610367 - 财政年份:2021
- 资助金额:
$ 4.49万 - 项目类别:
Mechanistic role of vascular dysfunction in TBI-mediated cognitive dysfunction
血管功能障碍在 TBI 介导的认知功能障碍中的机制作用
- 批准号:
10188260 - 财政年份:2021
- 资助金额:
$ 4.49万 - 项目类别:
Mechanistic role of vascular dysfunction in TBI-mediated cognitive dysfunction
血管功能障碍在 TBI 介导的认知功能障碍中的机制作用
- 批准号:
10391335 - 财政年份:2021
- 资助金额:
$ 4.49万 - 项目类别:
Brain injury rehabilitation modality, regulation, & structural plasticity
脑损伤康复方式、调节、
- 批准号:
9763360 - 财政年份:2018
- 资助金额:
$ 4.49万 - 项目类别:
Brain injury rehabilitation modality, regulation, & structural plasticity
脑损伤康复方式、调节、
- 批准号:
10226791 - 财政年份:2018
- 资助金额:
$ 4.49万 - 项目类别:
Brain injury rehabilitation modality, regulation, & structural plasticity
脑损伤康复方式、调节、
- 批准号:
10454815 - 财政年份:2018
- 资助金额:
$ 4.49万 - 项目类别:
Brain injury rehabilitation modality, regulation, & structural plasticity
脑损伤康复方式、调节、
- 批准号:
10670067 - 财政年份:2018
- 资助金额:
$ 4.49万 - 项目类别:
相似海外基金
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:
$ 4.49万 - 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:
$ 4.49万 - 项目类别:
Collaborative R&D
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:
$ 4.49万 - 项目类别:
Fellowship
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:
$ 4.49万 - 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:
$ 4.49万 - 项目类别:
Research 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:
$ 4.49万 - 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:
$ 4.49万 - 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:
$ 4.49万 - 项目类别:
Standard 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:
$ 4.49万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Acute human gingivitis systems biology
人类急性牙龈炎系统生物学
- 批准号:
484000 - 财政年份:2023
- 资助金额:
$ 4.49万 - 项目类别:
Operating Grants