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Na\u00efve astrocytes are readily converted to cytotoxic reactive astrocytes (A1) in response to inflammatory stimulation, suppressing the polarization of A1 protects against neuronal death in early central nervous system injury. Our previous study found that pro\u2010inflammatory cytokines and miR\u2010132\u20103p (hereinafter referred to as \u201cmiR\u2010132\u201d) expression were upregulated, but how miR\u2010132 affected reactive astrocyte polarization and neuronal damage during epilepsy is not fully understood. Here, we aimed to explore the effect and mechanism of miR\u2010132 on A1 polarization. Our results confirmed that A1 markers were significantly elevated in the hippocampus of MTLE rats and IL\u20101\u03b2\u2010treated primary astrocytes. In vivo, knockdown of miR\u2010132 by lateral ventricular injection reduced A1 astrocytes, neuronal loss, mossy fiber sprouting, and remitted the severity of status epilepticus and the recurrence of spontaneous recurrent seizures. In vitro, the neuronal cell viability and axon length were reduced by additional treatment with A1 astrocyte conditioned media (ACM), and downregulation of astrocyte miR\u2010132 rescued the inhibition of cell activity by A1 ACM, while the length of axons was further inhibited. The regulation of miR\u2010132 on A1 astrocytes may be related to its target gene expression. Our results show that interfering with astrocyte polarization may be a breakthrough in the treatment of refractory epilepsy, which may extend to the research of other astrocyte polarization\u2010mediated brain injuries.<\/jats:p>","DOI":"10.1096\/fj.202200110rr","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T09:39:06Z","timestamp":1663321146000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Silencing of\n                    <scp>miR<\/scp>\n                    \u2010132\u20103p protects against neuronal injury following status epilepticus by inhibiting\n                    <scp>IL<\/scp>\n                    \u20101\u03b2\u2010induced reactive astrocyte (\n                    <scp>A1<\/scp>\n                    ) 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