- Meeting abstract
- Open access
- Published:
The effect of memantine on cerebral cortex tumor necrosis factor alpha exression in a rat model of acute hyperammonemia
Annals of General Psychiatry volume 9, Article number: S181 (2010)
Background
Literature suggests that proinflammatory mechanisms are implicated in the pathophysiology of hepatic encephalopathy. This is mainly caused by high circulating levels of ammonia (hyperammonemia-HA), due to liver failure [1, 2]. In addition, NMDA receptors are excessively activated during acute hyperammonemia and thus significally contribute to the brain damage [3]. In fact, blockage of this receptor type is beneficial in experimental models of acute hyperammonemia [3, 4]. The aim of this study is to assess the effect of memantine, a non-competitive NMDA receptor antagonist, on the expression of tumor necrosis factor alpha (TNF-α), a major proinflammatory cytokine, in the brain of a rat model of acute hyperammonemia.
Materials and methods
HA was induced in male Wistar rats by two consecutive ammonium acetate intraperitoneal (i.p.) injections of 12 and 8 mmol/kg respectively [2]. Another group of rats received memantine hydrochloride (20 mg/kg) 30 minutes before the first ammonium acetate injection, while control group received saline i.p. Rats were decapitated 30 minutes after the last injection and cerebral cortex TNF-α expression was determined with reverse transcription quantitative PCR.
Results
TNF-α expression in rat cerebral cortex was significantly elevated while the administration of memantine hydrochloride diminished its expression.
Conclusions
Memantine manages to compensate the induction of TNF-α, a major proinflammatory cytokine, by acute HA, in the cerebral cortex of rats. Further research is needed in order to determine if the effect of memantine may be attributed to the blockage of NMDA receptors and if it has a similar impact on the expression of other proinflammatory cytokines.
References
Jiang W, Desjardins P, Butterworth RF: Direct evidence for central proinflammatory mechanisms in rats with experimental acute liver failure: protective effect of hypothermia. J Cereb Blood Flow Metab. 2009, 29 (5): 944-952. 10.1038/jcbfm.2009.18.
Singh S, Koiri RK, Trigun SK: Acute and chronic hyperammonemia modulate antioxidant enzymes differently in cerebral cortex and cerebellum. Neurochem Res. 2008, 33 (1): 103-113. 10.1007/s11064-007-9422-x.
Rodrigo R, Cauli O, Boix J, ElMlili N, Agusti A, Felipo V: Role of NMDA receptors in acute liver failure and ammonia toxicity: therapeutical implications. Neurochem Int. 2009, 55 (1-3): 113-118. 10.1016/j.neuint.2009.01.007.
Kosenko E, Kaminski Y, Lopata O, Muravyov N, Felipo V: Blocking NMDA receptors prevents the oxidative stress induced by acute ammonia intoxication. Free Radic Biol Med. 1999, 26 (11-12): 1369-1374. 10.1016/S0891-5849(98)00339-6.
Author information
Authors and Affiliations
Rights and permissions
Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Tsartsalis, S., Tomos, C., Karanikola, T. et al. The effect of memantine on cerebral cortex tumor necrosis factor alpha exression in a rat model of acute hyperammonemia. Ann Gen Psychiatry 9 (Suppl 1), S181 (2010). https://doi.org/10.1186/1744-859X-9-S1-S181
Published:
DOI: https://doi.org/10.1186/1744-859X-9-S1-S181