近期的研究发现脑缺血损伤以后脑内以及外周过度激活的免疫炎症反应不仅是早期神经功能损伤的重要致病因素，而且给后期神经功能的修复带来了极大的阻力。我们以往的研究发现通过移植小鼠自然形成的调节性T细胞可抑制脑缺血再灌注损伤后的血脑屏障破坏，从而抑制免疫炎症反应，可起到早期的神经保护作用。由于体内本身具有的自然形成调节性T细胞数量十分有限，本研究拟采用离体细胞体外扩增的方法获得更多数量的高纯度调节性T细胞。 通过长达28天的动物行为学测试以及脑梗死体积测定，验证离体扩增的调节性T细胞移植是否可对脑缺血损伤具有长期的神经保护作用。应用免疫荧光染色，激光共聚焦立体成像等技术，在重症联合免疫缺陷小鼠以及抗体中和中性粒细胞的小鼠中研究脑缺血后的神经血管单元重建，从而进一步深入地探讨脑内炎症反应与脑缺血后神经血管单元重建之间的关系，揭示离体扩增的调节性T细胞移植对脑缺血保护作用的潜在作用机制。

Recent studies reveal that cerebral ischemia elicits a profound inflammatory response. Overactivated peripheral immune cells panetrated to the brain paranchyma and not only severely impact stroke pathology in the early stage after ischemia but also hinder the neuronal repair in the long term. In our previous study, we found that tranplantation of natural occuring regulatory T cells(Tregs) could protect against the disruption of blood brain barrier and cerebral inflammation following ischemia. Because Tregs only account for 5% of total T cells, to obtain enough Tregs, we intended to expand Tregs ex vivo in this study. Using long term behavirial tests and brain infarct volume quantification, we will evaluate the neuroprotective effect of transplantation of ex vivo expanded Tregs in cerebral ischemia in mice. Reconstruction of neurovascular unit is recently implicated as an important process in the long term brain repair following ischemia. Cerebral inflammation was evidenced as a negative factor in the reconstraction of neurovascular unit. Therefore, in this study, we would like to test whether the long term protection afforded by Treg transplantation was mediated by inhibiting cerebral inflammation and subsequant enhanced neurogenesis and angiogenesis, which are two major components of neurovascular unit reconstruction. In this study, we will assess the neurogenesis and angiogenesis using immununofluorescence staining and confocal microscopy imaging in severe combined immune difficiency (SCID) mice or neurophil depleted mice. Hopefully, these experiments will reveal the potential mechanisms involved in the long term protection afforded by Treg transplantion in cerebral ischemic injury.