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.

摘要 神经影像学方法是非常宝贵的管理治疗中风病人在急性期的指导 再灌注和挽救组织，并且越来越多地用于了解 指导慢性期脑功能恢复的治疗。至少有一定程度的功能恢复 在大多数患者中风后的几个月内广泛观察到。指导这一过程的确切生物机制 正在积极调查恢复情况。BOLD功能磁共振成像（fMRI）和功能近 红外光谱（fNIRS），这两种非侵入性测量血管对大脑活动的反应， 这是在恢复期间对中风患者进行纵向监测的宝贵工具。然而，这些血管 在缺血性中风损伤的脑区域中，对外部刺激的反应几乎总是相对于 在中风和健康人的大脑区域的对侧。目前尚不清楚这是否 改变是神经元功能的潜在差异的反映，或者仅仅是神经元功能受损的结果。 血管改变血管对活动的反应。换句话说，我们不知道中风对 神经血管耦合，因此限制了我们使用这些有价值的神经成像工具来研究 中风幸存者的功能恢复。众所周知，中风会触发显著的血管重组， 梗死周围皮质的神经血管单位改变。目前尚不清楚这种血管的效率是否 重组有助于梗死周围皮质的神经生理学恢复，以及它是否与 最终的功能性成果。此外，尚不清楚梗死周围神经血管单位是否发生变化， 血流质量是潜在的神经恢复的简单反映，或者可以是随后的神经恢复的主要决定因素。 神经重组因此，很有必要对已建立并适当控制的 临床前中风模型，以评估慢性中风的结构和功能方面的演变， 神经血管恢复，以便更好地理解这些生物相互作用的机制， 了解它们对预测中风后行为结果的预后价值。我们的目标是 通过使用光学技术和临床前中风模型的新组合来满足这些需求。我们首先 建立中风纵向成像新技术的实用性。我们将利用这些 发现血流动力学恢复特征与毛细血管血流失速的关联的方法。最后我们 研究这些变化的异质性的机械解释。