Protective effects of regulatory T cells on ischemic brain damage

有机阳离子转运体3 （= OCT3）被确定为摄取2转运体，负责清除组胺。由于越来越多的证据表明组胺参与脑缺血，我们研究了靶向破坏OCT3对缺血性脑损伤严重程度的影响。阻断oct3纯合子缺失小鼠及其野生型仔鼠大脑中动脉，引起短暂局灶性缺血1小时。因此，靶向破坏OCT3可显著增加缺血皮质的组胺含量，并显著减少脑缺血后的梗死体积。此外，这种破坏阻止了脑缺血后调节性T细胞比例的减少。由于对野生型小鼠反复给予l -组氨酸（组胺的前体）也显示出相同的效果，我们的观察表明，OCT3是负责清除脑缺血诱导组胺的分子，靶向破坏OCT3可以通过增加调节性T细胞来改善缺血性脑损伤。

The organic cation transporters 3 (= OCT3) was identified as an uptake-2 transporter, responsible for clearance of histamine. Because increasing evidence suggests the involvement of histamine in cerebral ischemia, we investigated the effects of targeted disruption of OCT3 on the severity of ischemic brain damage. Transient focal ischemia for 1 hour was induced by occlusion of the middle cerebral artery (MCA) of homozygous Oct3-deficient mice and their wild type littermates. Consequently, targeted disruption of OCT3 significantly increased histamine content in the ischemic cortex and significantly reduced the infarct volume after cerebral ischemia. Furthermore, this disruption prevented the reduction of regulatory T cell proportion after cerebral ischemia. Since repeated administration of L-histidine (a precursor of histamine) to wild-type mice also showed the same effects, our observations suggested that OCT3 is the molecule responsible for clearance of ischemia-induced histamine in the brain and targeted disruption of OCT3 ameliorated ischemic brain damage through an increase in regulatory T cells.