The relationship between neuronal activity and stroke

神经元活动与中风的关系

• 批准号: 10585313
• 负责人: RON D FROSTIG
• 金额: $ 48.64万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-15 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10585313
• 关键词: Acoustic Stimulation; Address; Adult; Anatomy; Anesthesia procedures; Animal Model; Architecture; Auditory area; Behavior assessment; Blood flow; Cause of Death; Complement; Complementary therapies; Development; Dorsal; Early treatment; Electrophysiology (science); Female; Functional Imaging; Head; Histologic; Histology; Hour; Human; Hybrids; Image; Imaging Techniques; Infarction; Intervention Studies; Ischemia; Ischemic Stroke; Lateral; Lidocaine; Location; Machine Learning; Maps; Microelectrodes; Middle Cerebral Artery Occlusion; Modeling; Neurons; Outcome; Pharmacological Treatment; Play; Population; Rattus; Research; Rest; Role; Sensory; Series; Sodium Channel Blockers; Stroke; Stroke Volume; Structure; Tactile; Techniques; Testing; Vibrissae; artery occlusion; awake; disability; experimental study; gray matter; histological studies; in vivo; machine learning algorithm; male; middle cerebral artery; multimodality; neurovascular; novel; pre-clinical; programs; spatiotemporal; tactile stimulation; translational potential; young adult

Stroke is the one of the leading causes for death and the leading cause of long-term disability in the USA, and most strokes originate from blood flow blockage known as ischemic stroke. Since the majority of cortical ischemic strokes originate from blockage in the middle cerebral artery (MCA), our lab has studied stroke protection in a rat model of permanent middle cerebral artery occlusion (pMCAo). Our findings have demonstrated that sensory stimulation in the early 2 hours following pMCAo is protective but later (3-4 hours) the same stimulation becomes damaging (known as infarct). It is assumed that the location and volume of either the damaged or protected territory depends on the spatial structure of the occluded artery (e.g., MCA), but research results in our lab point to an alternative hypothesis that the location and volume of an infarcted or protected territory depends on the spread of evoked neuronal activity in cortex. To address our hypothesis, we plan to apply state-of-the-art multi-modal battery of in vivo wide-field imaging techniques including blood flow imaging and functional imaging of cortical activity. These imaging techniques are complemented by optogentic stimulation, electrophysiological recordings using microelectrode arrays, histological, pharmacological treatment studies, and by the development of machine learning algorithms. These techniques will be employed to provide an unprecedented spatiotemporal, quantitative understanding on how the spread of evoked activity is pivotal for predicating the location and volume of the infarcted or protected cortical territory. Finally, to increase the translational potential of these studies, these techniques will be applied in old rats that represent the population most vulnerable to stroke, and in awake, head-fixed young and old rats to increase the translational potential of our research.

在美国，中风是死亡的主要原因之一，也是长期残疾的主要原因， 并且大多数中风起源于称为缺血性中风的血流阻塞。因为大多数皮质 缺血性中风起源于大脑中动脉（MCA）阻塞，我们的实验室研究了中风 在永久性大脑中动脉闭塞（pMCAo）大鼠模型中的保护作用。我们的研究结果 表明pMCAo后早期2小时内的感觉刺激具有保护作用，但随后（3 - 4小时） 同样的刺激会造成损害（称为梗塞）。据推测，无论是位置和体积 受损或受保护的区域取决于闭塞动脉的空间结构（例如，MCA），但 我们实验室的研究结果指出了另一种假设，即梗塞或 受保护的领土取决于皮层中诱发的神经元活动的传播。 为了解决我们的假设，我们计划应用最先进的体内宽场成像的多模态电池 技术包括血流成像和皮质活动功能成像。这些成像技术 通过光遗传刺激，使用微电极阵列的电生理记录， 组织学、药理学治疗研究，以及机器学习算法的发展。 这些技术将被用来提供一个前所未有的时空，定量的了解 关于诱发活动的传播如何对于预测梗死灶的位置和体积至关重要， 受保护的皮层区域。最后，为了增加这些研究的转化潜力，这些技术 将应用于老年大鼠，代表人口最容易中风，并在清醒，头部固定 年轻和年老的大鼠来增加我们研究的转化潜力。