| Murine cerebral malaria is associated with a vasospasm-like microcirculatory dysfunction, and survival upon rescue treatment is markedly increased by nimodipine. | |
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MedLine Citation:
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PMID: 20110412 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Brain hemodynamics in cerebral malaria (CM) is poorly understood, with apparently conflicting data showing microcirculatory hypoperfusion and normal or even increased blood flow in large arteries. Using intravital microscopy to assess the pial microvasculature through a closed cranial window in the murine model of CM by Plasmodium berghei ANKA, we show that murine CM is associated with marked decreases (mean: 60%) of pial arteriolar blood flow attributable to vasoconstriction and decreased blood velocity. Leukocyte sequestration further decreased perfusion by narrowing luminal diameters in the affected vessels and blocking capillaries. Remarkably, vascular collapse at various degrees was observed in 44% of mice with CM, which also presented more severe vasoconstriction. Coadministration of artemether and nimodipine, a calcium channel blocker used to treat postsubarachnoid hemorrhage vasospasm, to mice presenting CM markedly increased survival compared with artemether plus vehicle only. Administration of nimodipine induced vasodilation and increased pial blood flow. We conclude that vasoconstriction and vascular collapse play a role in murine CM pathogenesis and nimodipine holds potential as adjunctive therapy for CM. |
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Authors:
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Pedro Cabrales; Graziela M Zanini; Diana Meays; John A Frangos; Leonardo J M Carvalho |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-01-28 |
Journal Detail:
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Title: The American journal of pathology Volume: 176 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-10 Completed Date: 2010-06-07 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 1306-15 Citation Subset: AIM; IM |
Affiliation:
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La Jolla Bioengineering Institute, 505 Coast Boulevard South Suite 406, La Jolla, CA 92037, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Artemisinins / pharmacology, therapeutic use Arterioles / drug effects, pathology, physiopathology Body Temperature / drug effects Cell Adhesion / drug effects Cerebrovascular Circulation / drug effects Erythrocytes / drug effects, parasitology, pathology Leukocytes / drug effects, parasitology Malaria, Cerebral / complications, drug therapy*, parasitology, physiopathology* Mice Mice, Inbred C57BL Microcirculation / drug effects, physiology* Nimodipine / pharmacology, therapeutic use* Parasitemia / complications, drug therapy, parasitology, physiopathology Plasmodium berghei / drug effects, physiology Survival Analysis Vasoconstriction / drug effects Vasodilation / drug effects Vasospasm, Intracranial / complications, drug therapy*, parasitology, physiopathology* |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL087290-02/HL/NHLBI NIH HHS; R01-HL87290/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Artemisinins; 0/artemether; 66085-59-4/Nimodipine |
| Comments/Corrections | |
Comment In:
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Am J Pathol. 2010 Mar;176(3):1075-8
[PMID:
20093501
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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