Department of Neurology, University Hospital Essen, Essen, Germany; Center for Translational and Behavioral Neurosciences, University Hospital Essen, Essen, Germany.
Institute for Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany.
Brain Behav Immun. 2022 Feb;100:134-144. doi: 10.1016/j.bbi.2021.11.016. Epub 2021 Nov 27.
Moderate dietary protein restriction confers neuroprotection when applied before ischemic stroke. How a moderately protein-reduced diet influences stroke recovery when administered after stroke, is a clinically relevant question. This question has not yet been investigated.
Male C57BL6/J mice were exposed to transient intraluminal middle cerebral artery occlusion. Immediately after the stroke, mice were randomized to two normocaloric diets: a moderately protein-reduced diet containing 8% protein (PRD) or normal diet containing 20% protein (ND). Post-stroke neurological deficits were evaluated by a comprehensive test battery. Antioxidant and neuroinflammatory responses in the brain and liver were evaluated by Western blot and RTqPCR. Stroke-induced brain injury, microvascular integrity, glial responses, and neuroplasticity were assessed by immunohistochemistry. Fecal microbiota analysis was performed using 16S ribosomal RNA amplicon sequencing.
We show that PRD reduces brain infarct volume after three days and enhances neurological and, specifically, motor-coordination recovery over six weeks in stroke mice. The recovery-promoting effects of PRD were associated with increased antioxidant responses and reduced neuroinflammation. Histochemical studies revealed that PRD increased long-term neuronal survival, increased peri-infarct microvascular density, reduced microglia/macrophage accumulation, increased contralesional pyramidal tract plasticity, and reduced brain atrophy. Fecal microbiota analysis showed reduced bacterial richness and diversity in ischemic mice on ND starting at 7 dpi. PRD restored bacterial richness and diversity at these time points.
Moderate dietary protein restriction initiated post-ischemic stroke induces neurological recovery, brain remodeling, and neuroplasticity in mice by mechanisms involving antiinflammation and, in the post-acute phase, commensal gut microbiota rebalancing.
中度的蛋白质限制饮食在缺血性中风前应用可提供神经保护。当在中风后给予中度蛋白质减少的饮食时，它如何影响中风后的恢复，这是一个具有临床相关性的问题。这个问题尚未得到研究。
雄性 C57BL6/J 小鼠接受短暂的管腔内大脑中动脉闭塞。中风后，立即将小鼠随机分为两种等热量饮食：含有 8%蛋白质的中度蛋白质减少饮食（PRD）或含有 20%蛋白质的正常饮食（ND）。通过综合测试套件评估中风后的神经缺损。通过 Western blot 和 RTqPCR 评估大脑和肝脏中的抗氧化和神经炎症反应。通过免疫组织化学评估中风引起的脑损伤、微血管完整性、神经胶质反应和神经可塑性。使用 16S 核糖体 RNA 扩增子测序进行粪便微生物组分析。
我们表明，PRD 可减少中风后 3 天的脑梗死体积，并在中风小鼠中增强神经功能，特别是运动协调的恢复超过 6 周。PRD 的恢复促进作用与增加的抗氧化反应和减少的神经炎症有关。组织化学研究表明，PRD 增加了长期神经元存活、增加了梗死周边的微血管密度、减少了小胶质细胞/巨噬细胞积累、增加了对侧皮质脊髓束可塑性，并减少了脑萎缩。粪便微生物组分析显示，在 ND 组缺血性小鼠的肠道微生物多样性在中风后 7 天开始减少。PRD 在这些时间点恢复了细菌丰富度和多样性。
在缺血性中风后开始的中度饮食蛋白质限制通过涉及抗炎的机制以及在急性期后，通过共生肠道微生物群的再平衡，诱导小鼠的神经恢复、脑重塑和神经可塑性。
