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.

中风是死亡的主要原因之一，也是美国长期残疾的主要原因， 大多数中风源自被称为缺血性中风的血流阻滞。由于大多数皮质 缺血性中风起源于中部大脑动脉（MCA）的阻塞，我们的实验室研究了中风 永久性大脑中动脉闭塞（PMCAO）的大鼠模型中的保护。我们的发现有 证明PMCAO后2小时的感官刺激具有保护性，但以后（3-4小时） 相同的刺激变成破坏性（称为梗塞）。假定任何一个的位置和音量 受损或受保护的领土取决于阻塞动脉的空间结构（例如MCA），但 研究导致我们的实验室指出了另一种假设，即梗塞或 受保护的领土取决于诱发的神经元活性在皮质中的传播。 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电池 包括血流成像和皮质活性功能成像的技术。这些成像技术 通过微观电极阵列进行了光量刺激，电生理记录的补充， 组织学，药理治疗研究以及通过机器学习算法的发展。 这些技术将用于提供前所未有的时空，定量理解 关于诱发活性的传播如何关键地涉及梗塞的位置和体积 受保护的皮质区域。最后，为了增加这些研究的翻译潜力，这些技术 将应用于代表最容易中风的人口的老鼠 年轻的和老鼠，以提高我们研究的翻译潜力。