The formation of inflammatory demyelinated lesions in cerebral white matter. Issue 4 (21st August 2014)

• Record Type: Journal Article
• Authors: Maggi, Pietro; Macri, Sheila M. Cummings; Gaitán, María I.; Leibovitch, Emily; Wholer, Jillian E.; Knight, Heather L.; Ellis, Mary; Wu, Tianxia; Silva, Afonso C.; Massacesi, Luca; Jacobson, Steven; Westmoreland, Susan; Reich, Daniel S.
• Is Part Of: Annals of neurology. Volume 76:Issue 4(2014:Oct.)
• Page Start: 594
• Page End: 608
• Publication Date: 2014-08-21
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.24242
• Languages: English
• ISSNs: 0364-5134

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ana24242-sec-0001" sec-type="section"> <title>Objective</title> <p>Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset.</p> </sec> <sec id="ana24242-sec-0002" sec-type="section"> <title>Methods</title> <p>By 7T magnetic resonance imaging (MRI), T1 maps, proton density, and T2‐weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood–brain barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination.</p> </sec> <sec id="ana24242-sec-0003" sec-type="section"> <title>Results</title> <p>On average, BBB permeability increased 3.5‐fold (<italic>p</italic> < 0.0001) over the 4 weeks prior to lesion appearance. Permeability gradually decreased after lesion appearance, with attendant changes in the distribution of inflammatory cells (predominantly macrophages and microglia) and demyelination. On tissue analysis, we also identified small perivascular foci of microglia and T cells without blood‐derived macrophages or demyelination. These foci had no visible MRI correlates, although permeability within the foci, but not outside, increased in the weeks before the animals died (<italic>p</italic> < 0.0001).</p> </sec> <sec id="ana24242-sec-0004" sec-type="section"> <title>Interpretation</title> <p>This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood‐derived monocytes that accompany demyelination. Prospective detection of transient permeability changes could afford an opportunity for early intervention to forestall tissue damage in newly forming lesions. Ann Neurol 2014;76:594–608</p> </sec> </abstract>