Brain Stimulation in Animal Models of Recovery from Acute Brain Injury

急性脑损伤动物模型中的脑刺激恢复

• 批准号: 9144415
• 负责人: Denis E. Bragin
• 金额: $ 24.01万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9144415
• 关键词: Acute; Acute Brain Injuries; Address; American; Animal Model; Area; Brain; Brain Injuries; Caregivers; Caring; Cell Count; Cells; Cerebrovascular Circulation; Cessation of life; Clinical; Clinical Research; Cognitive; Control Animal; Development; Effectiveness; Emotional; Evaluation; Face; Future; Genetic; Goals; Image; Imaging Techniques; Immigration; Infarction; Injury; Intervention; Label; Lasers; Life; Long-Term Effects; Maps; Membrane; Mental disorders; Methods; Modeling; Motor; Mus; Neurologic; Neurological outcome; New Mexico; Outcome; Outpatients; Perfusion; Persons; Phase; Phenotype; Public Health; Recovery; Recovery of Function; Reperfusion Therapy; Reporting; Research; Societies; Stem cells; Stimulus; Stroke; Survivors; Synapses; Synaptic plasticity; Testing; Therapeutic; Time; Traumatic Brain Injury; Traumatic Brain Injury recovery; Universities; Work; base; behavioral outcome; cerebrovascular; clinical application; cognitive function; contrast imaging; controlled cortical impact; cost; effective therapy; functional disability; improved; improved functioning; injured; migration; mouse model; nerve stem cell; nervous system disorder; neurobehavioral test; neurovascular coupling; novel therapeutics; optical imaging; relating to nervous system; repaired; research study; social; stem; two-photon

SUMMARY Traumatic brain injury (TBI) is a major public health problem in the U.S. which causes 30% of all injury related deaths and 7% long-term functional disabilities in survivors. Currently, 5.3 million Americans are living with permanent functional disabilities resulting from TBI with an estimated lifetime care cost of $4 million per person. New, effective treatments for TBI, especially for the late or recovery phase are urgently needed. Transcranial direct current stimulation (tDCS) has emerged as a promising therapeutic approach, and has recently been investigated as a clinical intervention for TBI. However, due to a lack of controlled animal studies, there are many important questions that need to be addressed to determine the utility of tDCS in TBI, and to refine the intervention to optimize long-term outcomes. These questions include the time windows for intervention and stimulus polarity for application. It is also unknown whether tDCS stimulates endogenous recovery and repair mechanisms that could in future studies be targeted to further enhance the effectiveness of tDCS in TBI survivors. The work in this proposal will address these key unanswered questions, to provide a basis for evaluation and future development of clinical interventions. Our central hypothesis is that tDCS applied in the recovery phase after TBI improves long-term neurologic recovery and is associated with increased migration of endogenous neuronal stem cells (NSC) to peri-infarct regions, and sustained increases in cerebral blood flow (CBF). A mouse controlled cortical impact model of TBI will be used, and repetitive tDCS treatment applied at one and three weeks after TBI. Specific Aim 1 will use a battery of advanced neurobehavioral tests for evaluation stimulus parameters and polarity and intervention time to the effects of tDCS on longitudinal improvement of neurological outcome. Specific Aim 2 will use a genetic labeling approach to assess the effects of tDCS on the migration tracking and long term phenotypic fate mapping of endogenous neural stem cells and their progeny. Specific Aim 3 will use optical imaging techniques to assess effects of tDCS on regional and microvascular cerebral circulation. Together, these studies will provide a valuable basis for improved understanding of the effects of tDCS in recovering brain, and for future refinement clinical applications.

摘要 在美国，创伤性脑损伤(TBI)是一个主要的公共健康问题，占所有与脑损伤有关的伤害的30% 存活者死亡和7%的长期功能残疾。目前，530万美国人与 颅脑损伤导致的永久性功能残疾，估计每名患者的终身护理费用为400万美元 人。迫切需要新的、有效的治疗方法来治疗创伤性脑损伤，特别是晚期或恢复期的脑损伤。 经颅直流电刺激(Tdcs)已成为一种很有前途的治疗方法。 近年来被研究作为脑外伤的一种临床干预措施。然而，由于缺乏受控动物， 研究表明，要确定tdcs在脑损伤中的效用，有许多重要的问题需要解决， 并改进干预措施，以优化长期结果。这些问题包括 干预性和刺激性应用。Tdcs是否刺激内源性也是未知的。 恢复和修复机制，可在今后的研究中有针对性地进一步提高 脑外伤存活者的TDCs。本提案中的工作将解决这些关键的未回答问题，以提供 为临床干预措施的评价和未来发展奠定基础。我们的中心假设是tdcs 在颅脑损伤后的恢复期应用可改善长期神经恢复，并与 内源性神经干细胞(NSC)向梗死区周围迁移增加，并持续增加 脑血流量(CBF)。将使用鼠标控制的脑损伤皮质撞击模型，并重复tdcs 分别于伤后1周和3周进行治疗。特定目标1将使用先进的电池 神经行为测试用于评估刺激参数和极性以及干预时间对其的影响 TDC对神经功能恢复的纵向改善作用。《特定目标2》将使用基因标记方法 评价tdcs对内源基因迁移追踪和长期表型归宿图谱的影响 神经干细胞及其后代。具体目标3将使用光学成像技术来评估 TDCs对局部和微血管脑循环的影响。总之，这些研究将提供有价值的基础。 为了更好地了解tdcs在脑复苏中的作用，并为未来的临床改进提供参考。 申请。