Introduction: Hepatic encephalopathy (HE) is a major neurological complication of severe liver disease. Recent studies have shown a significant role of neuroinflammation in the pathogenesis of both acute and chronic HE. There are different reports that HE is primarily induced by hyperammonemia and brain inflammation followed by liver failure. Mitogen-activated protein (MAP) kinases are key molecules in the signaling pathways of inflammatory and neurotransmitter receptors. It has been reported that MAP kinases are affected at transcriptional and post-transcriptional levels in the HE in response to inflammation induced by hyperammonemia. In recent years, porous materials have used as drug carriers. Nanoporous silica type SBA-15 is likely to absorb increased levels of ammonia in HE and reduce the amount of ammonia in the blood. This, in turn, can reduce the effects of ammonia and activate the pathway of cytokine receptors such as MAP-kinases in HE. The aim of this study was to evaluate the effect of subcutaneous injection of SBA-15 silicate nanoparticles in rat model of HE in order to investigate the possible therapeutic effects of these nanoparticles and the mechanisms of these therapeutic effects. Methods: Male Wistar rats weighing 300-350 g were used. Chronic liver failure was induced using a common bile duct ligation (BDL) in a group of rats as a model of HE. Sham control operation consisted of laparotomy and bile duct identification without ligation and resection. SBA nonporous (0.2 mg/kg) was injected subcutaneously every 48 hours during 28 days after BDL. The brain tissue samples from the prefrontal cortex (PFC) and the hippocampus were dissected, extraction of total RNA was done and real-time qPCR method was used to evaluate gene expression of p38 MAP kinase. Results: The results showed that in the hippocampus and PFC of the HE model rats, p38 gene expression was increased while the jnk3 gene expression was significantly decreased. Interestingly, SBA-15 nonporo
