Background: Subarachnoid hemorrhage (SAH) is a severe neurological condition with high mortality and morbidity rates, often exacerbated by secondary complications such as inflammation, cerebral vasospasm, and apoptosis. Proinflammatory cytokines, including interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), play critical roles in these pathological processes. Anakinra, an IL-1 receptor antagonist, has demonstrated significant anti-inflammatory effects in various disease models. This study aimed to evaluate the efficacy of anakinra in mitigating inflammation, vasospasm, and apoptosis in an experimental rat model of SAH. Methods: Thirty-two male Sprague Dawley rats were divided into four groups: Control (healthy), SAH (no treatment), Saline (0.2 mL saline subcutaneously), and Anakinra (50 mg/kg subcutaneously, twice daily). Proinflammatory markers (CRP, TNF-α, IL-1, IL-6, and fibrinogen) were measured in serum and cerebrospinal fluid (CSF) at 3, 7, and 10 days post-SAH. Basilar artery diameter was evaluated histopathologically, and Caspase-3 expression was assessed immunohistochemically to determine apoptotic activity. Results: SAH significantly increased levels of CRP, TNF-α, IL-1, IL-6, and fibrinogen in both serum and CSF, reduced basilar artery diameter, and elevated Caspase-3 expression compared to the Control group. Saline treatment provided limited improvements, with inflammatory markers and histopathological parameters remaining elevated. Anakinra treatment significantly reduced inflammatory markers, restored basilar artery diameter, and lowered Caspase-3 expression, highlighting its efficacy in mitigating inflammation, vasospasm, and apoptosis. Conclusions: Anakinra effectively suppresses inflammation, alleviates cerebral vasospasm, and inhibits apoptosis in an experimental model of SAH. These findings suggest its potential as a therapeutic agent for managing SAH and its complications. Further research is needed to explore its clinical applicability and long-term effects.

Objective: Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular condition that triggers a robust inflammatory response and cerebral vasospasm. This study aimed to evaluate the effects of anakinra, an interleukin-1 receptor antagonist, and tocilizumab, an interleukin-6 receptor antagonist, on inflammation and vasospasm in an experimental rat SAH model. Methods: Forty male Sprague Dawley rats (200–250 g) were randomly assigned to five groups: control, SAH, SAH + anakinra (ANA), SAH + tocilizumab (TCZ), and SAH + anakinra + tocilizumab (ANA+TCZ). SAH was induced by injecting non-heparinized arterial blood into the cisterna magna. Treatment groups received anakinra (50 mg/kg twice daily), tocilizumab (8 mg/kg once daily), or their combination for three days. Blood and cerebrospinal fluid (CSF) samples were analyzed for inflammatory markers (IL-1, IL-6, TNF-α, CRP), and histopathological evaluations were conducted to assess vasospasm and apoptosis. Results: SAH significantly increased pro-inflammatory cytokines (IL-1, IL-6, TNF-α, CRP) and fibrinogen levels in serum and CSF while reducing the basilar artery lumen diameter (p < 0.001). Anakinra and tocilizumab treatments significantly reduced inflammatory markers and vasospasm severity compared to the SAH group (p < 0.05). Combination therapy was more effective in reducing inflammation and vasospasm than either treatment alone (p < 0.05). Anakinra showed a stronger effect on IL-1 reduction, while tocilizumab was more effective in lowering IL-6 levels. The ANA+TCZ group exhibited a significant decrease in caspase activity, indicating reduced apoptosis (p < 0.05). Conclusions: Anakinra and tocilizumab effectively mitigated inflammation and vasospasm in an experimental SAH model, with combination therapy showing superior efficacy. These findings suggest that targeting both IL-1 and IL-6 pathways may be a promising therapeutic strategy for managing SAH complications. Further studies are warranted to evaluate long-term outcomes and clinical implications.