Pioglitazone mitigates early brain injury by suppressing neuroinflammation and oxidative stress after subarachnoid hemorrhage: a rodent model study.

OBJECTIVE

Subarachnoid haemorrhage (SAH) is a devastating neurovascular emergency where outcomes are largely driven by early brain injury (EBI). Neuroinflammation and oxidative stress are central to EBI pathogenesis. This study experimentally evaluated whether pioglitazone attenuates inflammatory and oxidative responses in the early phase after SAH.

MATERIALS AND

METHODS

Thirty-two adult male Sprague-Dawley rats were randomly allocated to four groups (n = 8/group): Sham, SAH, SAH+pioglitazone (PIO), and SAH+vehicle (VEH). SAH was induced by autologous blood injection into the cisterna magna. Pioglitazone (10 mg/kg, intraperitoneally) was administered 1 h post-SAH. Serum interleukin-6 (IL-6), interleukin-1β (IL-1β), and malondialdehyde (MDA) levels were quantified by Enzyme-Linked Immunosorbent Assay (ELISA) at 24 h. Hippocampal neuronal injury was assessed using semi-quantitative histopathological analysis of haematoxylin-eosin-stained sections. Acute-phase biochemical and histopathological effects were evaluated; long-term functional outcomes were not assessed.

RESULTS

IL-6, IL-1β, and MDA levels were significantly elevated in all SAH groups compared with sham (p < 0.001). Pioglitazone significantly reduced IL-6 compared with SAH (p = 0.032) and VEH (p = 0.049), though levels remained higher than sham. Conversely, IL-1β and MDA levels in the PIO group were significantly lower than in SAH and VEH (p = 0.001 and p = 0.002, respectively) and were comparable to sham. Histopathological analysis demonstrated significantly lower hippocampal neuronal degeneration scores in the pioglitazone-treated group (p < 0.05).

CONCLUSION

Early post-SAH administration of pioglitazone suppresses systemic inflammation and lipid peroxidation while mitigating hippocampal neuronal injury. These findings support a potential neuroprotective role of pioglitazone in EBI after SAH, likely mediated via peroxisome proliferator-activated receptor-γ (PPAR-γ) activation.