Evaluation of the effects of Eserine and JWH-133 on brain dysfunction associated with experimental endotoxemia

被引:13
作者
Gamal, Maha [1 ]
Moawad, Jackline [1 ]
Rashed, Laila [2 ]
El-Eraky, Wafaa [3 ]
Saleh, Dalia [3 ]
Lehmann, Christian [4 ,5 ,6 ,7 ,8 ]
Sharawy, Nivin [1 ,4 ,5 ,6 ]
机构
[1] Cairo Univ, Fac Med, Dept Physiol, Cairo, Egypt
[2] Cairo Univ, Fac Med, Dept Biochem, Cairo, Egypt
[3] Natl Res Ctr, Dept Pharmacol, Cairo, Egypt
[4] Dalhousie Univ, Fac Med, Dept Anesthesia, Halifax, NS B3H 2Y9, Canada
[5] Dalhousie Univ, Fac Med, Dept Pain Management, Halifax, NS B3H 2Y9, Canada
[6] Dalhousie Univ, Fac Med, Dept Perioperat Med, Halifax, NS B3H 2Y9, Canada
[7] Dalhousie Univ, Fac Med, Dept Microbiol & Immunol, Halifax, NS B3H 2Y9, Canada
[8] Dalhousie Univ, Dept Pharmacol, Fac Med, Halifax, NS B3H 2Y9, Canada
关键词
Sepsis; Cognitive; Behaviour; JWH-133; Eserine; TERM COGNITIVE IMPAIRMENT; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; P-GLYCOPROTEIN EXPRESSION; CENTRAL-NERVOUS-SYSTEM; NECROSIS-FACTOR-ALPHA; LONG-TERM; MICROGLIAL ACTIVATION; PARKINSONS-DISEASE; WORKING-MEMORY; SEVERE SEPSIS;
D O I
10.1016/j.jneuroim.2015.02.008
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Sepsis is associated with neuronal damage and cognitive impairment, with the participation of pro-inflammatory cytokines and oxidative-nitrous stress. It is Imown that activated microglia plays a vital role in neuro-inflammation and neuro-degeneration. Thus, the objective of this study was to evaluate therapeutic roles of two microglia regulating agents, JWH-133 and Eserine, on the neuroinflammatory associated brain dysfunctions. To achieve our aim, we used control rats or submitted rats to lipopolysaccharide (LPS) challenge. 30 min after LPS challenge, the animals received either saline, Eserine, JWH-133 or Eserine + JWH-133. After 24 h, animals were submitted to the habituation to T maze, Rotarod and activity cage tests. The rats were killed after and were evaluated for central and peripheral inflammatory and oxidative parameters. We observed that the use of Eserine, JWH-133 or Eserine + JWH-133 reverted the increases in the inflammatory markers [interleukin 6 (IL6), vascular cell adhesion molecule 1 (VCAM-1) and Eselectin] and oxidative-nitrous stress MDM, and that the anti-inflammatory, antioxidant properties of both JVVH-133 and Eserine successfully improve the LPS induced brain dysfunction. Conclusions: The results observed in this study reinforce the role of microglia activation regulating agents, in particular, JWH-133 and Eserine, in the brain dysfunction associated with endotoxemia. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:9 / 16
页数:8
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