Department of Physiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Cardiology of the Second Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Brain Behav Immun. 2024 Jan;115:705-717. doi: 10.1016/j.bbi.2023.11.023. Epub 2023 Nov 20.
Pericyte is an indispensable cellular constituent of blood-brain barrier (BBB) and its homeostasis heavily rely on PDGFB-PDGFRβ signaling. However, the primary cellular sources of PDGFB in the central nervous system (CNS) are unclear. Microglia is not considered a component of BBB and its role in maintaining BBB integrity in steady state is controversial. In this study, by analyzing transcriptomic data and performing in situ hybridization, we revealed a transition of the primary central PDGFB producers from endothelial cells in newborns to microglia in adults. Acute loss of microglial PDGFB profoundly impaired BBB integrity in adult but not newborn mice, and thus, adult mice deficient of microglial PDGFB could not survive from a sublethal endotoxin challenge due to rampant microhemorrhages in the CNS. In contrast, acute abrogation of endothelial PDGFB had minimal effects on the BBB of adult mice but led to a severe impairment of CNS vasculature in the neonates. Moreover, we found that microglia would respond to a variety of BBB insults by upregulating PDGFB expression. These findings underscore the physiological importance of the microglia-derived PDGFB to the BBB integrity of adult mice both in steady state and under injury.
周细胞是血脑屏障（BBB）不可或缺的细胞成分，其稳态严重依赖 PDGFB-PDGFRβ信号。然而，中枢神经系统（CNS）中 PDGFB 的主要细胞来源尚不清楚。小胶质细胞不被认为是 BBB 的组成部分，其在维持 BBB 完整性方面的作用存在争议。在这项研究中，通过分析转录组数据和进行原位杂交，我们揭示了主要的中枢 PDGFB 产生细胞从新生儿的内皮细胞向成年期的小胶质细胞的转变。小胶质细胞 PDGFB 的急性缺失会严重损害成年期而非新生小鼠的 BBB 完整性，因此，缺乏小胶质细胞 PDGFB 的成年小鼠由于中枢神经系统中广泛的微出血而无法从亚致死性内毒素挑战中存活下来。相比之下，内皮细胞 PDGFB 的急性缺失对成年小鼠的 BBB 几乎没有影响，但会导致新生鼠的中枢血管严重受损。此外，我们发现小胶质细胞会通过上调 PDGFB 表达来响应各种 BBB 损伤。这些发现强调了小胶质细胞衍生的 PDGFB 对成年期小鼠 BBB 完整性的生理重要性，无论是在稳态还是损伤情况下。
