Imaging neurodegeneration in multiple sclerosis

多发性硬化症的神经变性影像学

基本信息

批准号：
9270631
负责人：
PETER A CALABRESI
金额：
$ 35.44万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9270631
关键词：
Acute Angiography Animals Atrophic Autopsy Back Blood-Retinal Barrier Brain Brain region Clinical Data Demyelinations Disease Disease Progression Dropout Etiology Evaluation Extravasation Eye Fluorescein Functional disorder Ganglion Cell Layer Image Immune Inflammation Inner Nuclear Layer Inner Plexiform Layer Lesion Link Magnetic Resonance Imaging Measures Mediating Methods Modeling Multiple Sclerosis Myelin Nerve Degeneration Neurologic Neurons Nuclear Ophthalmic examination and evaluation Ophthalmology Optic Nerve Transections Optic Neuritis Optical Coherence Tomography Optics Outcome Pathology Patients Pattern Permeability Phenotype Predisposition Process Quality of life Radiology Specialty Recruitment Activity Resolution Retina Retinal Retinal Degeneration Site Societies Structure Swelling Testing Thick Thinness Time Waxes axon injury cerebral atrophy cohort cost disability experimental study gray matter imaging biomarker in vivo insight multiple sclerosis patient neuron loss new technology novel optic nerve disorder premature public health relevance retina outer nuclear layer retinal nerve fiber layer tomography white matter white matter injury

项目摘要

DESCRIPTION (provided by applicant): There is emerging evidence that gray matter (GM) degeneration is common in multiple sclerosis (MS), and more closely linked with disability than white matter (WM) injury. Indeed, WM volumes, as measured by high resolution MRI, wax and wane as a reflection of inflammation, whereas GM atrophy accelerates with time in MS. Whether GM degeneration purely results from WM injury or may also occur as a primary process in MS is unclear. More recently there has been growing evidence that primary neuronal loss in the cortex and retina may occur in MS, independent of demyelination or axonal injury. The retina, although an unmyelinated brain structure, is now recognized to be a frequent site of inflammation, blood-retinal-barrier disruption, and neuronal loss in MS, highlighting the retina as an opportune site to study the mechanisms by which inflammation directly mediates neurodegeneration in MS, and link these processes back to what is occurring in the brain. However, the interplay between changes in retinal layers over time, and the relationships of these changes with brain-substructure changes in MS remains unclear, and we propose to investigate this in the current application. Herein, we hypothesize that ONL atrophy is the consequence of INL inflammation, and signifies increased susceptibility for global neurodegeneration in MS as a consequence of inflammation. The completion of the experiments outlined in this application will reveal novel insights into the pathobiological mechanisms through which inflammation mediates neurodegeneration in myelinated and unmyelinated regions of the brain in MS. Specifically, we plan to determine if primary neuronal mechanisms of pathology are operative in MS retina, and if this primary neuronopathy is predictive of GM atrophy and the accrual of clinical disability in MS. The results could provide evidence to challenge the paradigm that MS is a myelin dependant disorder, and directly impact present concepts of how to target degeneration and disease progression in MS.

描述（由申请人提供）：有新兴的证据表明，灰质（GM）变性在多发性硬化症（MS）中很常见，并且与残疾（WM）损伤更与残疾密切相关。实际上，通过高分辨率MRI，蜡和衰落测量的WM体积作为炎症的反射，而GM萎缩随着MS的时间加速。 GM变性是否纯粹是由于WM损伤引起的还是也可能是MS中的主要过程发生的。最近，越来越多的证据表明，在MS中，皮质和视网膜的原发性神经元丧失可能与脱髓鞘或轴突损伤无关。视网膜虽然是一种不髓鞘的大脑结构，但现在被认为是MS的频繁炎症部位，血液 - 视网膜障碍的破坏和神经元丧失的位置，重点介绍了视网膜研究炎症直接介导MS中神经退行性的机制的适当位置，并将这些过程链接回大脑中发生的过程。但是，随着时间的推移，视网膜层的变化之间的相互作用与这些变化与MS的变化的关系尚不清楚，我们建议在当前应用中进行调查。在本文中，我们假设ONL萎缩是INL炎症的结果，这表明由于炎症而增加了MS全球神经变性的易感性。该应用程序中概述的实验的完成将揭示对病理学机制的新见解，通过这些见解，炎症介导了MS中大脑的髓鞘和无毛状区域中的神经变性。具体而言，我们计划确定病理学的主要神经元机制在MS视网膜中是否有效，并且该原发性神经病是否可以预测GM萎缩和MS中临床障碍的应计。结果可以提供证据来挑战范式表明MS是一种髓磷脂依赖性疾病，并直接影响了如何靶向MS中的退化和疾病进展的当前概念。