PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of agpsychBioMed Centralbiomed central web sitesearchsubmit a manuscriptregisterthis articleAnnals of General Psychiatry
 
Ann Gen Psychiatry. 2010; 9(Suppl 1): S181.
Published online 2010 April 22. doi:  10.1186/1744-859X-9-S1-S181
PMCID: PMC2991871

The effect of memantine on cerebral cortex tumor necrosis factor alpha exression in a rat model of acute hyperammonemia

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. doi: 10.1038/jcbfm.2009.18. [PubMed] [Cross Ref]
  • 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. doi: 10.1007/s11064-007-9422-x. [PubMed] [Cross Ref]
  • 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. doi: 10.1016/j.neuint.2009.01.007. [PubMed] [Cross Ref]
  • 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. doi: 10.1016/S0891-5849(98)00339-6. [PubMed] [Cross Ref]

Articles from Annals of General Psychiatry are provided here courtesy of BioMed Central