Ver, this drug has not been tested against CM-associated brain injury. > 자유게시판

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Ver, this drug has not been tested against CM-associated brain injury. Since CM-associated brain injuries and AIS share similar pathophysiological features, we hypothesized that NRG-1 will reduce or prevent neuroinflammation and brain damage as well as improve survival in mice with late-stage experimental cerebral malaria (ECM). Methods: We tested the effects of NRG-1 on ECM-associated brain inflammation and mortality in P. berghei ANKA (PbA)-infected mice and compared to artemether (ARM) treatment; an antimalarial currently used in various combination therapies against malaria. Results: Treatment with ARM (25 mg/kg/day) effectively cleared parasites and reduced mortality in PbA-infected mice by 82 . Remarkably, NRG-1 therapy (1.25 ng/kg/day) significantly improved survival against ECM by 73 despite increase in parasite burden within NRG-1-treated mice. Additionally, NRG-1 therapy reduced systemic and brain pro-inflammatory factors TNFalpha, IL-6, IL-1alpha and CXCL10 and enhanced anti-inflammatory factors, IL-5 and IL-13 while decreasing leukocyte accumulation in brain microvessels. Conclusions: This study suggests that NRG-1 attenuates ECM-associated brain inflammation and injuries and may represent a novel supportive therapy for the management of CM. Keywords: Neuregulin-1 (NRG-1), Pro-inflammatory, Anti-inflammatory, Blood rain barrier (BBB), Inflammation, Plasmodium berghei ANKA PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/12958591 (PbA), Adjunctive therapy, Malaria, Cerebral malaria (CM), Brain injuryBackground Nearly 300 million persons each year are infected with Plasmodium falciparum (P. falciparum) infection, a subset of whom may develop severe anemia or a diffuse encephalopathy known as cerebral malaria (CM) [1]. CM accounts for 110,000 deaths annually in children and one in four survivors develop neurological complications* Correspondence: wsolomon@msm.edu; jstiles@msm.edu Equal contributors 1 Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA Full list of author information is available at the end of the article(cortical blindness, epilepsy, and monoparesis) and cognitive disability (speech deficits, working memory, and g]carbazole (Tetrahydro-2H-pyran-4-yl)hydrazine hydrochloride (S)-1-((S)-2-(3 executive function disability) [2-8]. Despite appropriate antimalarial treatment, mortality associated with (S)-tert-Butyl 6-(hydroxymethyl)-5-azaspiro[2.4]heptane-5-carboxylate CM may be as high as 30 in adults and 20 in children [7,9-11]. Thus, targeting parasite in acute disease is not sufficient to ameliorate persistent neurological sequelae and mortality associated with CM. Understanding immunopathogenic features such as brain inflammation and injury leading to fatal CM have led to the identification and development of small molecules or PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/17591728 immunotherapeutics?2014 Solomon et al.; licensee BioMed Central Ltd. 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.Solomon et al. Journal of Neuroinflammation 2014, 11:9 http://www.jneuroinflammation.com/content/11/1/Page 2 ofthat may be used to stabilize the blood rain barrier (BBB) and ameliorate CM-associated 4-((2-Hydroxyethyl)(methyl)amino)benzaldehyde brain damage and mortality [12-14]. However, most of these interventions administered as prophylactics to prevent development.