Atorvastatin Ameliorates Neuroinflammatory Response in Experimental Intracerebral Hemorrhage Rats through the GSK-3β/β-Catenin Pathway
Jing Zhao1, Mei Li1, Lingling Zhang1, Qi Zhang1★★ Corresponding author
- 1Department of Neurology, Nantong RICH Hospital, Nantong, Jiangsu, CHINA.
CORRESPONDENCE
Qi Zhang
Department of Neurology, Nantong RICH Hospital, Nantong, Jiangsu, CHINA.
Received: 06-12-2024; Revised: 24-02-2025; Accepted: 16-06-2025.
Volume 59, Issue 4 · pp. 1501–1510 · PUBLISHED 2025 · DOI: 10.5530/ijper.20250529
ABSTRACT
Objectives: This study aimed to elucidate influence of Atorvastatin (ATV) on the neuroinflammatory response in experimental Intracerebral Hemorrhage (ICH) through the GSK-3β/β-catenin Signaling Pathway (SPW). Materials and Methods: Forty-five rats were randomly rolled into Sham, ICH (established using the Fredrik methodology) and ATV intervention (ICH model+10 mg/kg ATV) groups, each comprising 15 rats. Neurological deficits in rats were assessed using the Garcia methodology. Brain Water Content (BWC) was measured via wet-dry methodology. Nissl staining was conducted to observe Brain Tissue (BT) histological changes and count undamaged neurons. Expression Levels (ELs) of β-catenin, GSK-3β and p-GSK-3β in BT were detected. Levels of Inflammatory Factors (IFs) Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-1β and IL-6 in rat cerebrospinal fluid were measured. Results: Relative to Sham group, ICH group exhibited decreased postoperative neurological behavior scores, β-catenin gene mRNA ELs and β-catenin protein levels, along with a reduction in the number of intact neurons (p<0.05). BT BWC, GSK-3β gene levels, p-GSK-3β and GSK-3β protein ELs were greatly increased, that is, p<0.05, while IL-6, IL-1β and TNF-α in cerebrospinal fluid were markedly elevated (p<0.05). In comparison to ICH group, ATV group showed increased neurological behavior scores, β-catenin gene mRNA levels and β-catenin protein levels, with an increase in the number of intact neurons (p<0.05). Moreover, BWC, GSK-3β gene mRNA ELs, p-GSK-3β and GSK-3β protein ELs, as well as IFs, were notably decreased (p<0.05). Conclusion: ATV, through regulation of the GSK-3β/β-catenin SPW, inhibits inflammatory reactions and cellular damage, thereby ameliorating neurological dysfunction and neuroinflammatory responses in experimental ICH rats.
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Zhao, J., Li, M., Zhang, L., & Zhang, Q. (2025). Atorvastatin Ameliorates Neuroinflammatory Response in Experimental Intracerebral Hemorrhage Rats through the GSK-3β/β-Catenin Pathway. Indian Journal of Pharmaceutical Education and Research, 59(4), 1501–1510. https://doi.org/10.5530/ijper.20250529
