Reactive astrogliosis has occurred after intracerebral hemorrhage (ICH). Leukemia inhibitory factor (LIF) can act as a modulator for glial gene expression. Signal transducer and activator of transcription 3 (STAT3) is a critical regulator of reactive astrogliosis. The present study tested whether endogenous LIF acted on ICH-induced reactive astrogliosis via the STAT3 signaling pathway. Rats were divided into three experimental groups: 1) Rats received either an ICH or a needle insertion (sham), 2) Rats received 100 ng LIF or an equal volume of phosphate-buffered saline (PBS) by direct infusion into the lateral ventricle (LV) after ICH, and 3) AG490 (0.25 mg/kg) was injected into the LV to block STAT3 signaling. Brains were perfused to identify proliferating cell nuclear antigen (PCNA)+/glial fibrillary acidic protein (GFAP)+nuclei. The expression of GFAP, LIF, LIF receptor (LIFR), glycoprotein 130 (gp130), and phospho-STAT3 (p-STAT3) was evaluated by immunohistochemistry and Western blot, respectively. After ICH, the number of the PCNA+/GFAP+ nuclei and the expression of GFAP, LIF, LIFR, gp130, and p-STAT3 were increased. Moreover, LIF increased the number of PCNA+/GFAP+ nuclei and the expression of GFAP, LIFR, gp130, and p-STAT3. The number of PCNA+/ GFAP+ nuclei and GFAP protein levels were attenuated markedly after inhibition of p-STAT3. Together, these data suggest that LIF contributes to ICH-related reactive astrogliosis via activation of STAT3 signaling.

Zhou, Yang, Cui, Tang, Zhong, Luo, Yang, Zhang, (2017). Leukemia Inhibitory Factor Contributes to Reactive Astrogliosis via Activation of Signal Transducer and Activator of Transcription 3 Signaling after Intracerebral Hemorrhage in Rats. Journal of neurotrauma, 2017 04;34(8):1658-1665. https://www.ncbi.nlm.nih.gov/pubmed/27825285