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Inflammation is a common component of acute injuries of the central nervous system (CNS) such as ischemia, and degenerative disorders such as Alzheimer's disease. Glial cells play important roles in local CNS inflammation, and an understanding of the roles for microRNAs in glial reactivity in injury and disease settings may therefore lead to the development of novel therapeutic interventions. Here, we show that the miR‐181 family is developmentally regulated and present in high amounts in astrocytes compared to neurons. Overexpression of miR‐181c in cultured astrocytes results in increased cell death when exposed to lipopolysaccharide (LPS). We show that miR‐181 expression is altered by exposure to LPS, a model of inflammation, in both wild‐type and transgenic mice lacking both receptors for the inflammatory cytokine TNF‐α. Knockdown of miR‐181 enhanced LPS‐induced production of pro …