An Experimental Infarct Targeting the Internal Capsule: Histopathological and Ultrastructural Changes
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Background: Stroke involving the cerebral white matter (WM) has increased in prevalence, but most experimental studies have focused on ischemic injury of the gray matter. This study was performed to investigate the WM in a unique rat model of photothrombotic infarct targeting the posterior limb of internal capsule (PLIC), focusing on the identification of the most vulnerable structure in WM by ischemic injury, subsequent glial reaction to the injury, and the fundamental histopathologic feature causing different neurologic outcomes. Methods: Light microscopy with immunohistochemical stains and electron microscopic examinations of the lesion were performed between 3 hours and 21 days post-ischemic injury. Results: Initial pathological change develops in myelinated axon, concomitantly with reactive change of astrocytes. The first pathology to present is nodular loosening to separate the myelin sheath with axonal wrinkling. Subsequent pathologies include rupture of the myelin sheath with extrusion of axonal organelles, progressive necrosis, oligodendrocyte degeneration and death, and reactive gliosis. Increase of glial fibrillary acidic protein (GFAP) immunoreactivity is an early event in the ischemic lesion. WM pathologies result in motor dysfunction. Motor function recovery after the infarct was correlated to the extent of PLIC injury proper rather than the infarct volume. Conclusions: Pathologic changes indicate that the cerebral WM, independent of cortical neurons, is highly vulnerable to the effects of focal ischemia, among which myelin sheath is first damaged. Early increase of GFAP immunoreactivity indicates that astrocyte response initially begins with myelinated axonal injury, and supports the biologic role related to WM injury or plasticity. The reaction of astrocytes in the experimental model might be important for the study of pathogenesis and treatment of the WM stroke.
Abstract
Background: Stroke involving the cerebral white matter (WM) has increased in prevalence, but most experimental studies have focused on ischemic injury of the gray matter. This study was performed to investigate the WM in a unique rat model of photothrombotic infarct targeting the posterior limb of internal capsule (PLIC), focusing on the identification of the most vulnerable structure in WM by ischemic injury, subsequent glial reaction to the injury, and the fundamental histopathologic feature causing different neurologic outcomes. Methods: Light microscopy with immunohistochemical stains and electron microscopic examinations of the lesion were performed between 3 hours and 21 days post-ischemic injury. Results: Initial pathological change develops in myelinated axon, concomitantly with reactive change of astrocytes. The first pathology to present is nodular loosening to separate the myelin sheath with axonal wrinkling. Subsequent pathologies include rupture of the myelin sheath with extrusion of axonal organelles, progressive necrosis, oligodendrocyte degeneration and death, and reactive gliosis. Increase of glial fibrillary acidic protein (GFAP) immunoreactivity is an early event in the ischemic lesion. WM pathologies result in motor dysfunction. Motor function recovery after the infarct was correlated to the extent of PLIC injury proper rather than the infarct volume. Conclusions: Pathologic changes indicate that the cerebral WM, independent of cortical neurons, is highly vulnerable to the effects of focal ischemia, among which myelin sheath is first damaged. Early increase of GFAP immunoreactivity indicates that astrocyte response initially begins with myelinated axonal injury, and supports the biologic role related to WM injury or plasticity. The reaction of astrocytes in the experimental model might be important for the study of pathogenesis and treatment of the WM stroke.
참고문헌 (38)
- Schneider AT, "Ischemic stroke subtypes : a population-based study of incidence rates among blacks and whites", Stroke, 35, pp.1552~1556 (2004)
- Hachinski VC, "Leuko-araiosis", Arch Neurol, 44, pp.21~23 (1987)
- Matsusue E, "White matter changes in elderly people: MR-pathologic correlations", Magn Reson Med Sci, 5, pp.99~104 (2006)
- Fu JH, "Extent of white matter lesions is related to acute subcortical infarcts and predicts further stroke risk in patients with first ever ischaemic stroke", J Neurol Neurosurg Psychiatry, 76, pp.793~796 (2005)
- Kim GM, "Extensive leukoaraiosis is associated with high early risk of recurrence after ischemic stroke", Stroke, 45, pp.479~485 (2014)
- Bailey EL, "Potential animal models of lacunar stroke: a systematic review", Stroke, 40, pp.e451~e458 (2009)
- He SQ, "Topographic organization of corticospinal projections from the frontal lobe : motor areas on the lateral surface of the hemisphere", J Neurosci, 13, pp.952~980 (1993)
- 이민철, "Stem Cell Dynamics in an Experimental Model of Stroke", 전남의대학술지, 47(2), pp.90~98 (2011), 의과학연구소
- Song S, "Early expressions of hypoxia-inducible factor 1alpha and vascular endothelial growth factor increase the neuronal plasticity of activated endogenous neural stem cells after focal cerebral ischemia", Neural Regen Res, 9, pp.912~918 (2014)
- Jang JW, "Melatonin reduced the elevated matrix metalloproteinase-9 level in a rat photothrombotic stroke model", J Neurol Sci, 323, pp.221~227 (2012)
- Liebigt S, "Effects of rehabilitative training and anti-inflammatory treatment on functional recovery and cellular reorganization following stroke", Exp Neurol, 233, pp.776~782 (2012)
- Bush EC, "The scaling of white matter to gray matter in cerebellum and neocortex", Brain Behav Evol, 61, pp.1~5 (2003)
- Kudo T, "Neuropathologic changes in the gerbil brain after chronic hypoperfusion", Stroke, 24, pp.259~264 (1993)
- He Z, "Experimental model of small deep infarcts involving the hypothalamus in rats: changes in body temperature and postural reflex", Stroke, 30, pp.2743~2751 (1999)
- Hughes PM, "Focal lesions in the rat central nervous system induced by endothelin-1", J Neuropathol Exp Neurol, 62, pp.1276~1286 (2003)
- Frost SB, "An animal model of capsular infarct: endothelin-1 injections in the rat", Behav Brain Res, 169, pp.206~211 (2006)
- Whitehead SN, "Interaction between a rat model of cerebral ischemia and beta-amyloid toxicity: inflammatory responses", Stroke, 36, pp.107~112 (2005)
- Souza-Rodrigues RD, "Inflammatory response and white matter damage after microinjections of endothelin-1 into the rat striatum", Brain Res, 1200, pp.78~88 (2008)
- Tanaka Y, "Experimental model of lacunar infarction in the gyrencephalic brain of the miniature pig: neurological assessment and histological, immunohistochemical, and physiological evaluation of dynamic corticospinal tract deformation", Stroke, 39, pp.205~212 (2008)
- Shibata M, "White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion", Stroke, 35, pp.2598~2603 (2004)
- Kim HS, "A rat model of photothrombotic capsular infarct with a marked motor deficit: a behavioral, histologic, and microPET study", J Cereb Blood Flow Metab, 34, pp.683~689 (2014)
- 김형석, "Time Point Expression of Apoptosis Regulatory Proteins in a Photochemically-Induced Focal Cerebral Ischemic Rat Brain", 전남의대학술지, 47(3), pp.144~149 (2011), 의과학연구소
- Swanson RA, "A semiautomated method for measuring brain infarct volume", J Cereb Blood Flow Metab, 10, pp.290~293 (1990)
- Lee KH, "Prognostic significance of neuronal marker expression in glioblastomas", Childs Nerv Syst, 28, pp.1879~1886 (2012)
- Kim JM, "Endoneurial microangiopathy of sural nerve in experimental vacor-induced diabetes", Ultrastruct Pathol, 26, pp.393~401 (2002)
- Donovan V, "Repeated mild traumatic brain injury results in long-term white-matter disruption", J Cereb Blood Flow Metab, 34, pp.715~723 (2014)
- Bashkatov AN, "Handbook of biomedical optics", pp.67~100 (2011), CRC Press
- Silver J, "Regeneration beyond the glial scar", Nat Rev Neurosci, 5, pp.146~156 (2004)
- Franke H, "Pathophysiology of astroglial purinergic signalling", Purinergic Signal, 8, pp.629~657 (2012)
- Sato Y, "White matter activated glial cells produce BDNF in a stroke model of monkeys", Neurosci Res, 65, pp.71~78 (2009)
- Carrera E, "Diaschisis: past, present, future", Brain, 137, pp.2408~2422 (2014)
- REF044557869Fulmer CG, "Astrocyte-derived BDNF supports myelin protein synthesis after cuprizone-induced demyelination", J Neurosci, 34, pp.8186~8196 (2014)
- Miyamoto N, "Astrocytes promote oligodendrogenesis after white matter damage via brain-derived neurotrophic factor", J Neurosci, 35, pp.14002~14008 (2015)
- Ramos-Cejudo J, "Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in subcortical ischemic stroke", Stroke, 46, pp.221~228 (2015)
- Sozmen EG, "A white matter stroke model in the mouse: axonal damage, progenitor responses and MRI correlates", J Neurosci Methods, 180, pp.261~272 (2009)
- He Z, "Definition of the anterior choroidal artery territory in rats using intraluminal occluding technique", J Neurol Sci, 182, pp.16~28 (2000)
- Karadottir R, "NMDA receptors are expressed in oligodendrocytes and activated in ischaemia", Nature, 438, pp.1162~1166 (2005)
- Bakiri Y, "Testing NMDA receptor block as a therapeutic strategy for reducing ischaemic damage to CNS white matter", Glia, 56, pp.233~240 (2008)