PPARa activation by fenofibrate confers neuroprotection in various CNS disorders such as traumatic brain injury and Parkinson��s disease. In addition, we have recently shown that fenofibrate also induces another family of antiinflammatory genes, namely the Cyp4fs that are involved in the metabolism of potent pro-inflammatory eicosanoid, LTB4 to the non-toxic Zoxazolamine 20-hydroxy LTB4. The induction of Cyp4fs results in increased metabolism of the inflammatory prompt LTB4 and confers neuroprotection against LPS mediated damage. Thus, induction of Cyp4fs by fenofibrate in brain plays an important role in regulating the inflammatory response. In the present study we examined the neuroprotective effect of fenofibrate using both in vitro and in vivo models of JEV infection and demonstrate the significant neuroprotection offered by fenofibrate through reduction of inflammation and viral replication. Total RNA was isolated from BV-2 cells or mouse brain cortex of mice using TRI reagent. Random hexamers were used for cDNA synthesis using High-Capacity cDNA Reverse Transcription Kit. Real-time PCR was performed on ABI 7500 sequence detection system using Power SYBR Green PCR Master Mix according to the manufacturer��s instructions. All reactions were carried out in triplicate and negative control without the template was also included. 18S rRNA was used as an internal control for normalization. Data was analyzed using the comparative threshold cycle method. The RNA levels of each gene were normalized to the respective 18S levels. Following normalization, relative mRNA values were normalized using one of the genes or treatment conditions. Dissociation curves were generated to check for the specificity of primers. The relative efficiency of each PCR reaction was calculated from the respective standard curve. The sequence of the primers used for quantitative real time-PCR, amplicon size, slope and relative Cinoxacin efficiencies of each reaction is mentioned in Table 1. We then examined the effect of fenofibrate in vivo, using a murine model of JEV infection, which is characterized by neurological deficits potentially resulting from the massive inflammatory response. In the current study we demonstrate that fenofibrate, a wellknown hypolipidemic drug when administered 4 days prior to JEV infection reduces mortality by 80% in a murine model of JEV infection and prevents neurological deficits in the surviving mice. Thus, fenofibrate could potentially be used as a prophylactic drug in endemic areas when clusters of JEV infections are seen in children, for example in the monsoon season. Fenofibrate has been used in children for treating hyperlipidemia associated with Niemann-Pick disease, to improve insulin sensitivity and mitochondrial function following burn injury and as anti-angiogenic agent in children with brain tumors among others. One of the side effects of the use of fenofibrate in adults is rhabdomyolosis, which is characterized by myalgia, weakness, dark urine and is a cause for acute renal failure. However, while the use of fenofibrate in children has been described, there is no report of the occurrence of rhabdomyolosis. Fenofibrate is known to cross BBB and its administration 4 days prior to and 10 days post infection, which was necessary for the therapeutic effect did not cause any weight loss. In earlier studies also the neuroprotective effect of fenofibrate could be seen in apoE null mice only after 14 days of treatment prior to onset of cerebral ischemia. PPARa is a member of ligand activated nuclear receptor family, which includes PPARb/d and PPARc.