The role of minocycline in inhibiting the formation of glial scars through the expression of CNTF, TGF-β1, and NF-κB p65 in traumatic brain injury model rats

Abstract

Objective Traumatic brain injury (TBI) is one of the causes of permanent disability. The formation of glial scar after TBI is thought to be a contributing factor to this permanent disability. Currently, there is no effective therapy and research is being conducted to find neuroprotectant therapy in TBI, it is proven that one of the drugs that has potential as a neuroprotectant is minocycline. With different target organs and diseases, minocycline can inhibit CNTF, TGF-β1, and NF-κB p65 which contribute to the formation of glial scar. Therefore, this study aims to determine the role of minocycline in inhibiting glial scar formation through CNTF, TGF-β1, and NF-κB p65 pathways in TBI rats. Methods A total of 16 rats were randomly divided into four groups: TBI, TBI + MNO1, TBI + MNO2, and TBI + MNO3. On day 0, rats were exposed to brain injury with a weight drop model, then treated with minocycline orally for 14 days, and observed for cognitive function through Novel Object Recognition (NOR) test on day 15. On the next day, the rats were decapitated, and the brain was taken for immunofluorescence double staining. The determination of signaling pathways was performed by observing immunofluorescence double staining of CNTF, TGF-β1, and NF-κB p65 in perilesional areas containing glial scar using a Confocal Laser Scanning Microscope (CLSM). Results Administration of minocycline in TBI rats with a weight drop model can improve cognitive disorders after 14 days. The mechanism of minocycline in inhibiting glial scar formation is characterized by a decrease in GFAP intensity in the perilesion area of the brain through CNTF and TGF-β1 signaling pathways at doses of 50 mg/kg and 100 mg/kg orally. Although NF-κB p65 is not inhibited by minocycline specifically, NF-κB p65 interacting with CNTF and TGF-β1 plays a role in the mechanism of glial scar inhibition by minocycline. Inhibition of glial scar formation by minocycline promotes a permissive environment for axon regeneration, resulting in cognitive improvement after day 14. Conclusion Minocycline plays a role in inhibiting glial scar formation through CNTF and TGF-β1 pathways in TBI model rats.