title: Evolution of inflammation and white matter injury in a model of transient focal ischemia.
abstract: After an ischemic stroke, there is a prolonged inflammatory response and secondary phase of injury that is more amenable to treatment than acute neurotoxicity. Surprisingly, little is known about temporal and spatial relationships between inflammation and white matter injury. Here, we quantified development of white matter damage, inflammation, and a glial limitans at 1, 3, and 7 days after transient ischemia in the rat striatum using immunohistochemistry. Quantitative analysis showed that decreased staining for myelin basic protein and increased staining for damaged myelin basic protein began in the core, coincided with neutrophil infiltration, and progressed outward over time. Axon damage (i.e. accumulation of amyloid precursor protein) began at the edge of the lesion, coinciding with substantial microglia/macrophage activation, and progressed into the core. During the 7 days, activated microglia/macrophages dramatically increased only in the core and edge of the lesion. Detailed spatial analyses revealed that activated microglia/macrophages that surrounded undamaged axon bundles did not express ED1, a marker of phagocytic cells, whereas those inside damaged bundles expressed ED1. These results imply different contributions of neutrophils and microglia/macrophages to white matter injury after ischemic stroke. The distinct localizations of activated microglia/macrophages imply complex signals that regulate their migration toward and infiltration of damaged white matter.
authors.affiliation: Toronto Western Research Institute, University Health Network, and Department of Physiology, University of Toronto, Toronto, Canada.
authors.forename: Iska
authors.initials: I
authors.lastname: Moxon-Emre
authors.forename: Lyanne C
authors.initials: LC
authors.lastname: Schlichter
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D020520:Brain Infarction / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002135:Calcium-Binding Proteins; D003342:Corpus Striatum / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D053331:Ectodysplasins / Q000378:metabolism; D007839:Functional Laterality / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008840:Microfilament Proteins; D004676:Myelin Basic Protein / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology*; D009457:Neuroglia / Q000473:pathology; D058255:Protease Nexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism; D013778:Tetrazolium Salts; D013997:Time Factors
chemical_list: C112986:AIF1 protein, human; D016564:Amyloid beta-Protein Precursor; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D053331:Ectodysplasins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D004676:Myelin Basic Protein; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D013778:Tetrazolium Salts