Vahabzadeh-Hagh Andrew, McCarthy Thomas J, De Taboada Luis, Streeter Jackson, Pascual-Leone Alvaro, Lo Eng H, Hayakawa Kazuhide
Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Cond Med. 2019 Aug;2(4):170-177.
Damage-associated molecular pattern signals may play key roles in mediating non-cell autonomous effects of pre and post-conditioning. Here, we show that near-infrared (NIR) light stimulation of astrocytes increases a calcium-dependent secretion of the prototypical DAMP, HMGB1, which may then accelerate endothelial progenitor cell (EPC) accumulation after stroke. Conditioned media from NIR-stimulated astrocytes increased EPC proliferation in vitro, and blockade of HMGB1 with siRNA diminished the effect. In vivo transcranial NIR treatment confirmed that approximately 40% of NIR could penetrate the scalp and skull. Concomitantly, NIR increased GFAP expression in normal mouse brain at 30 min after the irradiation. In a mouse model of focal ischemia, repeated irradiation of NIR at days 5, 9, and 13 successfully increased HMGB1 in peri-infarct cortex, leading to a higher accumulation of EPCs at 14 days post-stroke. Conditioning and tolerance are now known to involve cell-cell signaling between all cell types in the neurovascular unit. Taken together, our proof-of-concept study suggest that NIR light may be an effective conditioning tool to stimulate astrocytic signaling and promote EPC accumulation after stroke.
损伤相关分子模式信号可能在介导预处理和后处理的非细胞自主性效应中发挥关键作用。在此，我们表明近红外（NIR）光刺激星形胶质细胞会增加典型损伤相关分子模式蛋白HMGB1的钙依赖性分泌，进而可能加速中风后内皮祖细胞（EPC）的聚集。来自近红外刺激的星形胶质细胞的条件培养基在体外增加了EPC的增殖，而用小干扰RNA（siRNA）阻断HMGB1可减弱这种效应。体内经颅近红外治疗证实约40%的近红外光可穿透头皮和颅骨。同时，近红外光在照射后30分钟增加了正常小鼠大脑中胶质纤维酸性蛋白（GFAP）的表达。在局灶性缺血小鼠模型中，在第5、9和13天重复照射近红外光成功增加了梗死周围皮质中的HMGB1，导致中风后14天时EPC的更高聚集。现在已知预处理和耐受性涉及神经血管单元中所有细胞类型之间的细胞间信号传导。综上所述，我们的概念验证研究表明，近红外光可能是一种有效的预处理工具，可刺激星形胶质细胞信号传导并促进中风后EPC的聚集。
