Aris Widayati, Fedik Abdul Rantam, Abdulloh Machin, Wibi Riawan
Background/Aims: Simvastatin is recognized for its pleiotropic properties. Beyond its role in lowering lipid, it also affects brain function, especially under pathological conditions like ischemic stroke. Neurogenesis and the increased expression of ACAN and VCAN in glial scar are linked to ischemic stroke, with both ACAN and VCAN being regulated by the transcription factor Sox9.This study aimed to investigate the mechanism by which simvastatin inhibits ACAN and VCAN expression and promotes neurogenesis. Materials: Twenty male Wistar rats were randomly assigned to four groups: sham, P1, P2, and P3. The sham group consisted of rats with ischemic stroke that did not receive simvastatin, while groups P1, P2, and P3 are rats with ischemic stroke that received simvastatin at doses of 5 mg, 10 mg, and 15 mg/kg/day, respectively, for 7 consecutive days. Motor function was assessed using the LRWT test. The expression levels of ACAN, VCAN, BDNF, and SOX9 were analyzed using immunohistochemistry (IHC), while BDNF and SOX9 mRNA expression was measured via RT-PCR. Glial scar density was evaluated through hematoxylin and eosin staining. Results: The findings revealed that simvastatin administration led to improved motor function, along with increased levels of BDNF, BDNF mRNA, and a higher number of neurons. Additionally, there was a reduction in ACAN, VCAN, and glial scar density, which corresponded with decreased expression of SOX9 and SOX9 mRNA. Conclusion: These results suggest that simvastatin can suppress ACAN and VCAN expression and reduce glial scar formation by inhibiting SOX9. Moreover, simvastatin appears to promote neurogenesis, as indicated by elevated BDNF levels and an increased or(s). © 2025 Published The Author(s) by.
Doctoral Program Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Physiology, Faculty of Medicine, Universitas Brawijaya, Universitas Brawijaya Academic Hospital, Malang, Indonesia; Research Center for Vaccine Technology and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia; Virology and Immunology Laboratory, Department of Microbiology, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Neurology, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Hospital, Surabaya, Indonesia; Post Graduate Doctoral Program, Faculty of Medicine, Universitas Airlangga, Universitas Airlangga General Hospital, Surabaya, Indonesia; Department of Biomolecular Biochemistry, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
