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Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I

BACKGROUND: Metabolic stroke is the rapid onset of lasting central neurological deficit associated with decompensation of an underlying metabolic disorder. Glutaric aciduria type I (GA1) is an inherited disorder of lysine and tryptophan metabolism presenting with metabolic stroke in infancy. The cli...

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Autores principales: Zinnanti, William J, Lazovic, Jelena, Housman, Cathy, Antonetti, David A, Koeller, David M, Connor, James R, Steinman, Lawrence
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940023/
https://www.ncbi.nlm.nih.gov/pubmed/24468193
http://dx.doi.org/10.1186/2051-5960-2-13
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author Zinnanti, William J
Lazovic, Jelena
Housman, Cathy
Antonetti, David A
Koeller, David M
Connor, James R
Steinman, Lawrence
author_facet Zinnanti, William J
Lazovic, Jelena
Housman, Cathy
Antonetti, David A
Koeller, David M
Connor, James R
Steinman, Lawrence
author_sort Zinnanti, William J
collection PubMed
description BACKGROUND: Metabolic stroke is the rapid onset of lasting central neurological deficit associated with decompensation of an underlying metabolic disorder. Glutaric aciduria type I (GA1) is an inherited disorder of lysine and tryptophan metabolism presenting with metabolic stroke in infancy. The clinical presentation includes bilateral striatal necrosis and spontaneous subdural and retinal hemorrhages, which has been frequently misdiagnosed as non-accidental head trauma. The mechanisms underlying metabolic stroke and spontaneous hemorrhage are poorly understood. RESULTS: Using a mouse model of GA1, we show that metabolic stroke progresses in the opposite sequence of ischemic stroke, with initial neuronal swelling and vacuole formation leading to cerebral capillary occlusion. Focal regions of cortical followed by striatal capillaries are occluded with shunting to larger non-exchange vessels leading to early filling and dilation of deep cerebral veins. Blood–brain barrier breakdown was associated with displacement of tight-junction protein Occludin. CONCLUSION: Together the current findings illuminate the pathophysiology of metabolic stroke and vascular compromise in GA1, which may translate to other neurometabolic disorders presenting with stroke.
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spelling pubmed-39400232014-03-04 Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I Zinnanti, William J Lazovic, Jelena Housman, Cathy Antonetti, David A Koeller, David M Connor, James R Steinman, Lawrence Acta Neuropathol Commun Research BACKGROUND: Metabolic stroke is the rapid onset of lasting central neurological deficit associated with decompensation of an underlying metabolic disorder. Glutaric aciduria type I (GA1) is an inherited disorder of lysine and tryptophan metabolism presenting with metabolic stroke in infancy. The clinical presentation includes bilateral striatal necrosis and spontaneous subdural and retinal hemorrhages, which has been frequently misdiagnosed as non-accidental head trauma. The mechanisms underlying metabolic stroke and spontaneous hemorrhage are poorly understood. RESULTS: Using a mouse model of GA1, we show that metabolic stroke progresses in the opposite sequence of ischemic stroke, with initial neuronal swelling and vacuole formation leading to cerebral capillary occlusion. Focal regions of cortical followed by striatal capillaries are occluded with shunting to larger non-exchange vessels leading to early filling and dilation of deep cerebral veins. Blood–brain barrier breakdown was associated with displacement of tight-junction protein Occludin. CONCLUSION: Together the current findings illuminate the pathophysiology of metabolic stroke and vascular compromise in GA1, which may translate to other neurometabolic disorders presenting with stroke. BioMed Central 2014-01-27 /pmc/articles/PMC3940023/ /pubmed/24468193 http://dx.doi.org/10.1186/2051-5960-2-13 Text en Copyright © 2014 Zinnanti et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zinnanti, William J
Lazovic, Jelena
Housman, Cathy
Antonetti, David A
Koeller, David M
Connor, James R
Steinman, Lawrence
Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I
title Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I
title_full Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I
title_fullStr Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I
title_full_unstemmed Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I
title_short Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I
title_sort mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type i
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940023/
https://www.ncbi.nlm.nih.gov/pubmed/24468193
http://dx.doi.org/10.1186/2051-5960-2-13
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