Neurophotonic Advances for Mechanistic Investigation of the Role of Capillary Dysfunction in Stroke Recovery

毛细血管功能障碍在中风恢复中作用机制研究的神经光子学进展

• 批准号: 10586375
• 负责人: David A Boas
• 金额: $ 69.37万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-27 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10586375
• 关键词: Acute; Basement membrane; Behavioral; Binding; Biological; Blood Cells; Blood Vessels; Blood capillaries; Blood flow; Brain; Brain region; Calcium; Cell Adhesion Molecules; Cells; Chronic; Chronic Phase; Clinical; Conflict (Psychology); Coupling; Data; Elements; Endothelial Cells; Endothelium; Ensure; Event; Evolution; Exposure to; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Heterogeneity; Human; Image; Incidence; Individual; Infarction; Investigation; Ischemic Stroke; Lateral; Leukocytes; Link; Measures; Mechanics; Metabolic; Methodology; Methods; Modeling; Monitor; Neurons; Optical Coherence Tomography; Optics; Outcome; Oxygen; Patients; Pericytes; Phase; Population; Predictive Value; Recovery; Recovery of Function; Reperfusion Therapy; Role; Signal Transduction; Site; Solid; Speed; Stimulus; Stroke; Surface; Technology; Testing; Tissues; Variant; base; behavioral outcome; constriction; design; functional near infrared spectroscopy; functional outcomes; hemodynamics; improved; neuroimaging; neurophysiology; neurovascular; neurovascular coupling; neurovascular unit; neutrophil; new technology; novel; post stroke; pre-clinical; prognostic value; relating to nervous system; response; restoration; serial imaging; stroke model; stroke outcome; stroke patient; stroke recovery; stroke survivor; stroke therapy; tool; two photon microscopy

ABSTRACT Neuroimaging methods are invaluable for managing the treatment of stroke patients in the acute phase of guiding reperfusion and salvaging tissue, and are being used more and more to understand the effect of and ultimately guide treatments in the chronic phase of functional brain recovery. At least some degree of functional recovery is widely observed in most patients in the months following stroke. The exact biological mechanism directing this recovery is under active investigation. BOLD functional Magnetic Resonance Imaging (fMRI) and functional Near Infrared Spectroscopy (fNIRS), both of which non-invasively measure the vascular response to brain activity, are valuable tools for longitudinal monitoring of stroke patients during this recovery period. However, these vascular responses to external stimuli in brain regions damaged by ischemic stroke are almost always altered relative to that in brain regions contra-lateral to the stroke and to that seen in healthy individuals. It is not known if this alteration is a reflection of underlying differences in the neuronal function or simply a result of damaged vasculature altering the vascular response to activity. In other words, we do not know the effect of stroke on neurovascular coupling and are thus limited in our ability to use these valuable neuroimaging tools to study functional recovery in stroke survivors. It is known that stroke triggers a prominent vascular reorganization and neurovascular unit changes in the periinfarct cortex. It is not known whether the efficiency of this vascular reorganization contributes to the neurophysiological recovery of the periinfarct cortex, and whether it is linked to the final functional outcome. Further, it is not known whether periinfarct neurovascular unit changes and capillary flow quality are a simple reflection of underlying neural recovery or can be a primary determinant of subsequent neural reorganization. Therefore, there is a great need for studies in well-established and properly controlled preclinical stroke models to evaluate the evolution of the structural and functional aspects of chronic neurovascular recovery, for a better mechanistic understanding of these biological interactions, and to understand their prognostic value for predicting behavioral outcomes following stroke. Our aims are designed to meet these needs by using a novel combination of optical technologies and a preclinical stroke model. We first establish the utility of the novel technology for longitudinal imaging of stroke. We will then utilize these approaches to find the association of hemodynamic recovery signatures with capillary flow stalls. Finally, we investigate mechanistic explanations for the heterogeneity of these changes.

抽象的 神经影像学方法对于在引导的急性阶段管理中风患者的治疗是无价的 再灌注和挽救组织，并越来越多地用于了解并最终 在功能性脑恢复的慢性阶段的指导治疗。至少某种程度的功能恢复 在中风后的几个月中，大多数患者都广泛观察到。指导此的确切生物学机制 恢复正在积极调查中。大胆的功能磁共振成像（fMRI）和功能性附近 红外光谱法（FNIRS），这两种非侵入性测量对脑活动的血管反应是 在此恢复期间，有价值的工具用于对中风患者进行纵向监测。但是，这些血管 相对于缺血性中风损坏的大脑区域中外部刺激的反应几乎总是在改变 在大脑区域与中风和健康个体所见的那样。不知道这是否 改变是神经元功能中潜在差异的反映，或仅仅是受损的结果 脉管系统改变了对活性的血管反应。换句话说，我们不知道中风对 神经血管耦合，因此我们使用这些有价值的神经影像工具的能力有限 中风幸存者的功能恢复。众所周知，中风会触发突出的血管重组和 神经血管单元的围绕皮质的变化。尚不清楚该血管的效率是否 重组有助于周围皮质的神经生理恢复，以及它是否与 最终功能结果。此外，尚不清楚周围神经血管单元是否变化和毛细管 流量质量是基础神经恢复的简单反映，或者可能是随后的主要决定因素 神经重组。因此，需要在建立良好且正确控制的研究中进行研究 临床前中风模型，以评估慢性的结构和功能方面的演变 神经血管恢复，以更好地了解这些生物学相互作用，并 了解他们的预后价值，以预测中风后的行为结果。我们的目标旨在 通过使用光学技术和临床前中风模型的新型组合来满足这些需求。我们首先 建立新技术用于中风的纵向成像的实用性。然后，我们将利用这些 找到血液动力学恢复特征与毛细管流倒下的方法。最后，我们 研究这些变化异质性的机理解释。