颈内动脉高渗甘露醇使血脑屏障开放，引起非感染性炎症和固有免疫反应。
Blood-brain barrier opening by intracarotid artery hyperosmolar mannitol induces sterile inflammatory and innate immune responses.
机构信息
Frank Laboratory, Radiology and Imaging Sciences, NIH Clinical Center, Bethesda, MD 20895;
Department of Neurology, Oregon Health & Science University, Portland, OR 97239.
出版信息
Proc Natl Acad Sci U S A. 2021 May 4;118(18). doi: 10.1073/pnas.2021915118.
Intracarotid arterial hyperosmolar mannitol (ICAHM) blood-brain barrier disruption (BBBD) is effective and safe for delivery of therapeutics for central nervous system malignancies. ICAHM osmotically alters endothelial cells and tight junction integrity to achieve BBBD. However, occurrence of neuroinflammation following hemispheric BBBD by ICAHM remains unknown. Temporal proteomic changes in rat brains following ICAHM included increased damage-associated molecular patterns, cytokines, chemokines, trophic factors, and cell adhesion molecules, indicative of a sterile inflammatory response (SIR). Proteomic changes occurred within 5 min of ICAHM infusion and returned to baseline by 96 h. Transcriptomic analyses following ICAHM BBBD further supported an SIR. Immunohistochemistry revealed activated astrocytes, microglia, and macrophages. Moreover, proinflammatory proteins were elevated in serum, and proteomic and histological findings from the contralateral hemisphere demonstrated a less pronounced SIR, suggesting neuroinflammation beyond regions of ICAHM infusion. Collectively, these results demonstrate ICAHM induces a transient SIR that could potentially be harnessed for neuroimmunomodulation.
颈内动脉高渗甘露醇（ICAHM）血脑屏障破坏（BBBD）对于中枢神经系统恶性肿瘤的治疗药物输送是有效且安全的。ICAHM 通过改变血管内皮细胞和紧密连接的完整性来实现 BBBD。然而，ICAHM 引起的大脑半球 BBBD 后是否会发生神经炎症尚不清楚。ICAHM 后大鼠大脑的时间蛋白质组学变化包括增加的损伤相关分子模式、细胞因子、趋化因子、营养因子和细胞粘附分子，表明存在无菌性炎症反应（SIR）。蛋白质组学变化发生在 ICAHM 输注后 5 分钟内，并在 96 小时内恢复到基线。ICAHM BBBD 后的转录组学分析进一步支持了 SIR。免疫组织化学显示激活的星形胶质细胞、小胶质细胞和巨噬细胞。此外，血清中促炎蛋白水平升高，对侧大脑半球的蛋白质组学和组织学发现表明 SIR 程度较轻，提示 ICAHM 输注区域以外存在神经炎症。总之，这些结果表明，ICAHM 诱导短暂的 SIR，这可能被用于神经免疫调节。
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