Tenascin-C Facilitates Microglial Polarization via TLR4/MyD88/NF-κB Pathway Following Subarachnoid Hemorrhage.

PURPOSE: This study primarily aims to elucidate the underlying mechanism of Tenascin-C in neuroinflammation and microglia polarization in a mouse model of subarachnoid hemorrhage (SAH). METHODS: The subarachnoid hemorrhage model was constructed by injecting blood into the anterior chiasmatic cistern and stimulating primary microglia with hemoglobin in vitro. Then, Imatinib mesylate was used to inhibit Tenascin-C. Through neurological function scoring, brain edema, primary cell extraction, immunofluorescence staining, CCK8, Tunel staining, Elisa, Western blot and other methods, the potential mechanism of Tenascin-C induced microglia cell polarization was explored. RESULTS: The results of this study observed that the expression of Tenascin-C was up-regulated after subarachnoid hemorrhage. Inhibiting the increase of Tenascin-C by imatinib could significantly ameliorate neuroinflammation, neuronal apoptosis, blood brain barrier disruption and brain edema. When the level of Tenascin-C decreased, the numbers of TLR4 positive, MyD88 positive and NF-κB positive microglial cells decreased accordingly. Moreover, after subarachnoid hemorrhage, the number of microglial cells positive for M1-type markers increased significantly. After imatinib inhibited Tenascin-C, the number of M1-type microglial cells decreased and the number of M2-type microglial cells increased significantly. CONCLUSION: In summary, the elevated level of Tenascin-C after subarachnoid hemorrhage induces the activation of microglia, releasing a large number of inflammatory factors and aggravating early brain injury.