Intracerebral hemorrhage (ICH) is a devastating cerebrovascular associated with inflammation and BBB disruption. Pericytes plays a critical role in neurological diseases, while whether pericytes could be utilized to treat ICH remains to be elucidated. Here, we isolated CD146⁺CD34⁻ pericytes from rat adipose tissues (ADPs). Fluorescence-activated cells maintained their cell morphology and differentiation potential and expressed pericytes markers (CD146, NG2, and PDGFRβ) but not endothelial markers (CD31, CD34, and CD45). ADPs transplantation improved the neuro-behavioral functions in ICH rats and resulted in decreased hematoma volume and neuron loss after ICH. Besides, ADPs graft restrained the infiltration of neutrophils and reactive microgliosis after ICH injury around the peri-hematoma area of rats, as evidenced by increased Iba1- and MPO immunoreactivity. The transplanted pericytes were covered on endothelial cells, and promoted angiogenesis and vascular basement membrane formation in the peri-hematoma area of ICH rats, as shown by double staining of PDGFRβ and CD31/CollagenIV. The decreased brain water content and Evans Blue leakage proved the protective role of ADPs graft on BBB permeability. Finally, transplanted ADPs increased the expression of VE-cadherin, ZO-1, and claudin-5, leading to stable endothelial cell-cell adhesion and tight junction. In conclusion, the transplantation of APDs improved neuronal after ICH, which involved different mechanisms including neuroinflammation regulation and BBB dysfunction recovery. Our results supported that ADPs might be the ideal cell type for ICH therapy and provided insights into the potential cell therapy for further ICH treatment.

脑出血 (ICH) 是一种与炎症和血脑屏障破坏相关的破坏性脑血管疾病。周细胞在神经系统疾病中发挥着至关重要的作用，而周细胞是否可以用于治疗脑出血仍有待阐明。在这里，我们从大鼠脂肪组织（ADP）中分离出 CD146 ⁺ CD34 ^-周细胞。荧光激活的细胞保持其细胞形态和分化潜力，并表达周细胞标记物（CD146、NG2 和 PDGFRβ），但不表达内皮标记物（CD31、CD34 和 CD45）。ADPs 移植改善了 ICH 大鼠的神经行为功能，并减少了 ICH 后的血肿量和神经元损失。此外，ADPs 移植物抑制了大鼠血肿周围区域 ICH 损伤后中性粒细胞的浸润和反应性小胶质细胞增生，Iba1- 和 MPO 免疫反应性增加证明了这一点。PDGFRβ和CD31/CollagenIV双染色显示，移植的周细胞覆盖在内皮细胞上，促进ICH大鼠血肿周围区域的血管生成和血管基底膜形成。脑含水量的降低和伊文思蓝渗漏证明了ADPs移植物对血脑屏障通透性的保护作用。最后，移植的ADP增加了VE-钙粘蛋白、ZO-1和claudin-5的表达，从而导致稳定的内皮细胞-细胞粘附和紧密连接。总之，APDs 移植改善了 ICH 后的神经元，涉及不同的机制，包括神经炎症调节和 BBB 功能障碍恢复。我们的结果支持 ADP 可能是 ICH 治疗的理想细胞类型，并为进一步 ICH 治疗的潜在细胞疗法提供了见解。