Levetiracetam Reduces Early Inflammatory Response After Experimental Intracerebral Hemorrhage by Regulating the Janus Kinase 2 (JAK2)–Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathway

BACKGROUND: Levetiracetam (LEV) is an antiepileptic drug that promotes recovery of neurological function by alleviating inflammatory reactions. However, it is not known whether it can improve secondary brain injury after intracerebral hemorrhage (ICH). The aim of this study was to determine whether LEV can reduce early inflammatory response after ICH in rats. MATERIAL/METHODS: An in vitro model of early inflammation was created by treating microglia cells with lipopolysaccharide (LPS). After exposure to various concentrations of LEV, the expression levels of NF-κB and STAT3 and inflammatory factors such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α in microglia were detected. In vivo, autologous blood was used to induce the rat ICH model. The effects of LEV on post-cerebral hemorrhagic inflammatory response were examined using neurobehavioral tests, FJC staining, brain water content testing, and analysis of protein expression levels of NF-κB, JAK2, STAT3, and inflammatory factors. RESULTS: LEV treatment significantly reduced the expression of inflammatory factors and protein expression levels of NF-κB and STAT3 in LPS-treated microglia cells (P<0.05). In male Sprague-Dawley (SD) rats, LEV treatment markedly decreased the volume of hematoma and the number of degenerative neurons (P<0.05). It also improved the neurological function and relieved brain edema. The protein expression levels of NF-κB, JAK2, and STAT3 were significantly lower in the ICH+LEV group than in the control group (P<0.05). CONCLUSIONS: Our study suggests that treatment with LEV alleviates early inflammatory responses induced by ICH. Mechanistically, LEV inhibited the JAK2-STAT3 signaling pathway and reduced neuronal injury around the hematoma, and ameliorated brain edema, all of which promoted recovery of nerve function after hemorrhage.