Abstract：
Streptococcus pneumoniae (the pneumococcus) is the major cause of bacterial meningitis globally, and pneumococcal meningitis is associated with increased risk of long-term neurological sequelae. These include several sensorimotor functions that are controlled by specific brain regions which, during bacterial meningitis, are damaged by a neuroinflammatory response and the deleterious action of bacterial toxins in the brain. However, little is known about the invasion pattern of the pneumococcus into the brain. Using a bacteremia-derived meningitis mouse model, we combined 3D whole brain imaging with brain microdissection to show that all brain regions were equally affected during disease progression, with the presence of pneumococci closely associated to the microvasculature. In the hippocampus, the invasion provoked microglial activation, while the neurogenic niche showed increased proliferation and migration of neuroblasts. Our results indicate that, even before the outbreak of symptoms, the bacterial load throughout the brain is high and causes neuroinflammation and cell death, a pathological scenario which ultimately leads to a failing regeneration of new neurons.
摘要：
肺炎链球菌（肺炎球菌）是全球细菌性脑膜炎的主要原因，肺炎球菌性脑膜炎与长期神经系统后遗症的风险增加有关。这些包括几种由特定大脑区域控制的感觉运动功能，在细菌性脑膜炎期间，受到神经炎症反应和大脑中细菌毒素的有害作用的损害。然而,对肺炎球菌侵入大脑的模式知之甚少。使用菌血症衍生的脑膜炎小鼠模型，我们将3D全脑成像与脑显微解剖相结合，以显示所有大脑区域在疾病进展过程中受到同等影响，与微血管密切相关的肺炎球菌的存在。在海马中,入侵引发了小胶质细胞的激活，而神经源性生态位显示成神经细胞的增殖和迁移增加。我们的研究结果表明,甚至在症状爆发之前，整个大脑的细菌负荷很高，会导致神经炎症和细胞死亡，最终导致新神经元再生失败的病理情景。
