Immune Cells in the BBB Disruption After Acute Ischemic Stroke: Targets for Immune Therapy?
Immune Cells in the BBB Disruption After Acute Ischemic Stroke: Targets for Immune Therapy?
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急性缺血性中风后血脑屏障破坏中的免疫细胞：免疫治疗的目标？
DOI：
10.3389/fimmu.2021.678744
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发表时间：
2021
影响因子：
7.3
通讯作者：
Hu B
中科院分区：
文献类型：
--
作者：
Qiu YM;Zhang CL;Chen AQ;Wang HL;Zhou YF;Li YN;Hu B
血脑屏障（BBB）破坏是急性缺血性脑卒中（AIS）的重要病理生理过程，可导致毁灭性的恶性脑水肿和出血性转化。免疫细胞的快速激活在缺血性卒中后血脑屏障破坏中起着关键作用。渗透的血液免疫细胞（中性粒细胞、单核细胞和T淋巴细胞）增加BBB通透性，因为它们引起微血管疾病并分泌炎症相关分子。相反，它们在缺血性中风的后期促进BBB修复和血管生成。脑免疫细胞（小胶质细胞，星形胶质细胞和周细胞）对血脑屏障破坏的深刻免疫作用在缺血性卒中中被低估。中风后小胶质细胞和星形胶质细胞可以采用M1/A1或M2/A2表型，这两种表型对BBB完整性的影响不同。然而，周细胞是否获得小胶质细胞表型并对BBB发挥免疫作用仍存在争议。因此，更好地理解BBB破坏的炎症机制可以导致识别更有希望的生物靶点，以开发最大限度地减少危及生命的并发症的发生并改善患者现有治疗的治疗方法。然而，早期尝试通过阻断粘附分子来抑制循环免疫细胞向脑中的浸润，在实验性中风中取得成功，但在临床试验中失败了。因此，迫切需要新的免疫调节治疗策略来治疗急性缺血性卒中。在此，我们强调了循环和脑免疫细胞在血脑屏障破坏中的作用，以及急性缺血性卒中后它们之间的相互作用。使用一个强大的理论背景，我们讨论了潜在的和有效的免疫靶点，以调节血脑屏障通透性急性缺血性卒中后。
Blood-Brain Barrier (BBB) disruption is an important pathophysiological process of acute ischemic stroke (AIS), resulting in devastating malignant brain edema and hemorrhagic transformation. The rapid activation of immune cells plays a critical role in BBB disruption after ischemic stroke. Infiltrating blood-borne immune cells (neutrophils, monocytes, and T lymphocytes) increase BBB permeability, as they cause microvascular disorder and secrete inflammation-associated molecules. In contrast, they promote BBB repair and angiogenesis in the latter phase of ischemic stroke. The profound immunological effects of cerebral immune cells (microglia, astrocytes, and pericytes) on BBB disruption have been underestimated in ischemic stroke. Post-stroke microglia and astrocytes can adopt both an M1/A1 or M2/A2 phenotype, which influence BBB integrity differently. However, whether pericytes acquire microglia phenotype and exert immunological effects on the BBB remains controversial. Thus, better understanding the inflammatory mechanism underlying BBB disruption can lead to the identification of more promising biological targets to develop treatments that minimize the onset of life-threatening complications and to improve existing treatments in patients. However, early attempts to inhibit the infiltration of circulating immune cells into the brain by blocking adhesion molecules, that were successful in experimental stroke failed in clinical trials. Therefore, new immunoregulatory therapeutic strategies for acute ischemic stroke are desperately warranted. Herein, we highlight the role of circulating and cerebral immune cells in BBB disruption and the crosstalk between them following acute ischemic stroke. Using a robust theoretical background, we discuss potential and effective immunotherapeutic targets to regulate BBB permeability after acute ischemic stroke.
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影响因子：
82.9
作者：
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作者：
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通讯作者：
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影响因子：
3.7
作者：
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Trendelenburg G