Kılıç Güven, Engin Berk Enes, Halabi Amir, Tuncer Cengiz, Sungur Mehmet Ali, Alpay Merve, Kurtuluş Adem, Soylu Hakan, Gök Ali
Department of Neurosurgery, Faculty of Medicine, Duzce University, Duzce 81100, Türkiye.
Department of Biostatistics, Faculty of Medicine, Duzce University, Duzce 81100, Türkiye.
Medicina (Kaunas). 2024 Dec 9;60(12):2025. doi: 10.3390/medicina60122025.
: 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. : 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. : 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 ( < 0.001). Anakinra and tocilizumab treatments significantly reduced inflammatory markers and vasospasm severity compared to the SAH group ( < 0.05). Combination therapy was more effective in reducing inflammation and vasospasm than either treatment alone ( < 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 ( < 0.05). : 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.
蛛网膜下腔出血(SAH)是一种危及生命的脑血管疾病,会引发强烈的炎症反应和脑血管痉挛。本研究旨在评估白细胞介素-1受体拮抗剂阿那白滞素和白细胞介素-6受体拮抗剂托珠单抗对实验性大鼠SAH模型中炎症和血管痉挛的影响。:将40只雄性Sprague Dawley大鼠(200 - 250克)随机分为五组:对照组、SAH组、SAH +阿那白滞素(ANA)组、SAH +托珠单抗(TCZ)组和SAH +阿那白滞素+托珠单抗(ANA+TCZ)组。通过向小脑延髓池注射非肝素化动脉血诱导SAH。治疗组接受阿那白滞素(50毫克/千克,每日两次)、托珠单抗(8毫克/千克,每日一次)或它们的组合,持续三天。分析血液和脑脊液(CSF)样本中的炎症标志物(IL-1、IL-6、TNF-α、CRP),并进行组织病理学评估以评估血管痉挛和细胞凋亡。:SAH显著增加血清和CSF中促炎细胞因子(IL-1、IL-6、TNF-α、CRP)和纤维蛋白原水平,同时减小基底动脉管腔直径(<0.001)。与SAH组相比,阿那白滞素和托珠单抗治疗显著降低炎症标志物和血管痉挛严重程度(<0.05)。联合治疗在减轻炎症和血管痉挛方面比单独任何一种治疗都更有效(<0.05)。阿那白滞素对降低IL-1的作用更强,而托珠单抗在降低IL-6水平方面更有效。ANA+TCZ组的半胱天冬酶活性显著降低,表明细胞凋亡减少(<0.05)。:阿那白滞素和托珠单抗在实验性SAH模型中有效减轻炎症和血管痉挛,联合治疗显示出更高的疗效。这些发现表明,针对IL-1和IL-6途径可能是管理SAH并发症的一种有前景的治疗策略。有必要进行进一步研究以评估长期结果和临床意义。