1. Dexamethasone prevents motor deficits and neurovascular damage produced by shiga toxin 2 and lipopolysaccharide in the mouse striatum.
- Author
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Pinto A, Cangelosi A, Geoghegan PA, and Goldstein J
- Subjects
- Animals, Astrocytes drug effects, Astrocytes immunology, Astrocytes pathology, Blood-Brain Barrier drug effects, Blood-Brain Barrier immunology, Blood-Brain Barrier pathology, Capillary Permeability drug effects, Capillary Permeability physiology, Cerebrovascular Disorders etiology, Cerebrovascular Disorders immunology, Cerebrovascular Disorders pathology, Corpus Striatum blood supply, Corpus Striatum drug effects, Corpus Striatum immunology, Corpus Striatum pathology, Disease Models, Animal, Escherichia coli, Female, Mice, Microvessels drug effects, Microvessels immunology, Microvessels pathology, Motor Activity drug effects, Motor Activity physiology, Movement Disorders etiology, Movement Disorders immunology, Movement Disorders pathology, Neuroprotective Agents pharmacology, Anti-Inflammatory Agents pharmacology, Cerebrovascular Disorders drug therapy, Dexamethasone pharmacology, Lipopolysaccharides toxicity, Movement Disorders drug therapy, Shiga Toxin 2 toxicity
- Abstract
Shiga toxin 2 (Stx2) from enterohemorrhagic Escherichia coli (EHEC) causes bloody diarrhea and Hemolytic Uremic Syndrome (HUS) that may derive to fatal neurological outcomes. Neurological abnormalities in the striatum are frequently observed in affected patients and in studies with animal models while motor disorders are usually associated with pyramidal and extra pyramidal systems. A translational murine model of encephalopathy was employed to demonstrate that systemic administration of a sublethal dose of Stx2 damaged the striatal microvasculature and astrocytes, increase the blood brain barrier permeability and caused neuronal degeneration. All these events were aggravated by lipopolysaccharide (LPS). The injury observed in the striatum coincided with locomotor behavioral alterations. The anti-inflammatory Dexamethasone resulted to prevent the observed neurologic and clinical signs, proving to be an effective drug. Therefore, the present work demonstrates that: (i) systemic sub-lethal Stx2 damages the striatal neurovascular unit as it succeeds to pass through the blood brain barrier. (ii) This damage is aggravated by the contribution of LPS which is also produced and secreted by EHEC, and (iii) the observed neurological alterations may be prevented by an anti-inflammatory treatment., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2017
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