Donny Wisnu WARDHANA, Husnul KHOTIMAH, Tommy Alfandy NAZWAR, Nurdiana NURDIANA
Journal of Research in Pharmacy - 2025;29(6):2193-2205
Traumatic brain injury (TBI) often leads to permanent disability, with glial scar formation being a significant contributor. Despite ongoing research, effective therapies remain elusive. Minocycline, a potential neuroprotective, may inhibit glial scar formation by targeting CNTF, TGF-beta1, and NF-kappaB p65 pathways. This study investigates minocycline's role in preventing glial scar formation in TBI rats. Sixteen rats were divided into four groups: TBI, TBI + MNO1, TBI + MNO2, and TBI + MNO3. Following a brain injury using a weight drop model, rats were treated orally with minocycline for 14 days. Cognitive function was assessed via the Novel Object Recognition (NOR) test on day 15. The brains were then analyzed using immunofluorescence double staining to examine CNTF, TGF-beta1, and NF-kappaB p65 signaling pathways in perilesional areas. 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-beta1 signaling pathways at doses of 50 mg/kg and 100 mg/kg orally. Although NF-kappaB p65 is not inhibited by minocycline specifically, NF-kappaB p65 interacting with CNTF and TGF-beta1 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. Minocycline effectively inhibits glial scar formation through CNTF and TGF-beta1 pathways in TBI model rats.
