Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China.
Clinical Research Center for Neurological Diseases of Zhejiang Province, Hangzhou, China.
J Neuroinflammation. 2024 Sep 27;21(1):237. doi: 10.1186/s12974-024-03236-y.
Early severe cerebral edema and chronic hydrocephalus are the primary cause of poor prognosis in patients with subarachnoid hemorrhage (SAH). This study investigated the role of cerebrospinal fluid (CSF) inflammatory cytokines and coagulation factors in the development of severe cerebral edema and chronic hydrocephalus in patients with SAH.
Patients with SAH enrolled in this study were categorized into mild and severe cerebral edema groups based on the Subarachnoid Hemorrhage Early Brain Edema Score at admission. During long-term follow-up, patients were further classified into hydrocephalus and non-hydrocephalus groups. CSF samples were collected within 48 h post-SAH, and levels of inflammatory cytokines and coagulation factors were measured. Univariate and multivariate logistic regression analyses were performed to identify independent factors associated with severe cerebral edema and chronic hydrocephalus. The correlation between inflammatory cytokines and coagulation factors was further investigated and validated in a mouse model of SAH.
Seventy-two patients were enrolled in the study. Factors from the extrinsic coagulation pathway and inflammatory cytokines were associated with both severe cerebral edema and chronic hydrocephalus. Coagulation products thrombin-antithrombin complexes (TAT) and fibrin, as well as inflammatory cytokines IL-1β, IL-2, IL-5, IL-7, and IL-4, were independently associated with severe cerebral edema. Additionally, Factor VII, fibrin, IL-2, IL-5, IL-12, TNF-α, and CCL-4 were independently associated with chronic hydrocephalus. A positive correlation between extrinsic coagulation factors and inflammatory cytokines was observed. In the SAH mouse model, tissue plasminogen activator was shown to alleviate neuroinflammation and cerebral edema, potentially by restoring glymphatic-meningeal lymphatic function.
Elevated levels of inflammatory cytokines and extrinsic coagulation pathway factors in the CSF are associated with the development of early severe cerebral edema and chronic hydrocephalus following SAH. These factors are interrelated and may contribute to post-SAH glymphatic-meningeal lymphatic dysfunction.
蛛网膜下腔出血（SAH）患者早期严重脑水肿和慢性脑积水是预后不良的主要原因。本研究探讨了脑脊液（CSF）炎症细胞因子和凝血因子在 SAH 患者严重脑水肿和慢性脑积水发展中的作用。
根据入院时的蛛网膜下腔出血早期脑水肿评分，将本研究纳入的 SAH 患者分为轻度和重度脑水肿组。在长期随访中，患者进一步分为脑积水组和非脑积水组。在 SAH 后 48 小时内采集 CSF 样本，检测炎症细胞因子和凝血因子水平。采用单因素和多因素逻辑回归分析确定与严重脑水肿和慢性脑积水相关的独立因素。进一步在 SAH 小鼠模型中验证炎症细胞因子和凝血因子之间的相关性。
本研究纳入 72 例患者。外源性凝血途径和炎症细胞因子相关因素与严重脑水肿和慢性脑积水均相关。凝血产物凝血酶-抗凝血酶复合物（TAT）和纤维蛋白以及炎症细胞因子 IL-1β、IL-2、IL-5、IL-7 和 IL-4 与严重脑水肿独立相关。此外，因子 VII、纤维蛋白、IL-2、IL-5、IL-12、TNF-α和 CCL-4 与慢性脑积水独立相关。外源性凝血因子和炎症细胞因子之间存在正相关。在 SAH 小鼠模型中，组织型纤溶酶原激活物被证明可以减轻神经炎症和脑水肿，可能是通过恢复神经胶-脑膜淋巴功能。
CSF 中炎症细胞因子和外源性凝血途径因子水平升高与 SAH 后早期严重脑水肿和慢性脑积水的发生有关。这些因素相互关联，可能导致 SAH 后神经胶-脑膜淋巴功能障碍。
