迷走神经调节代谢稳态并介导肠-脑通信。我们假设迷走神经功能障碍,由截短迷走神经切断术(VGX)或颈动脉闭塞(AO)诱导,会破坏肠道-大脑的交流并加剧代谢失调,神经炎症,和认知障碍。这项研究旨在检验高脂饮食沙鼠的假设。沙鼠分为四组:AO与VGX(AO_VGX),不带VGX的AO(AO_NVGX),没有带VGX的AO(NAO_VGX),并且没有没有VGX的AO(NAO_NVGX)。在高脂肪饮食5周后,神经元细胞死亡,神经严重程度,海马脂质和炎症,能量/葡萄糖代谢,肠道形态学,和粪便微生物组组成进行评估。AO和VGX增加了神经元细胞死亡和神经严重程度评分,与海马脂质谱和脂质过氧化增加相关,以及炎性细胞因子表达和脑源性神经营养因子(BDNF)水平的变化。AO和VGX也增加了体重,内脏脂肪量,胰岛素抵抗和减少骨骼肌质量。肠道形态和微生物组组成发生改变,随着双歧杆菌丰度的增加和阿克曼西亚和Ruminococus的减少。微生物宏基因组功能也受到影响,包括谷氨酸能突触活动,糖原合成,和氨基酸生物合成。有趣的是,VGX对AO的影响不显著,表明AO抑制迷走神经活动,部分抵消了VGX的影响。总之,AO和VGX加剧了能量失调,葡萄糖,和脂质代谢,神经炎症,和记忆缺陷,可能通过调节肠脑轴。通过抑制迷走神经抑制靶向肠-脑轴代表了缺血性中风的潜在治疗策略。
The vagus nerve regulates metabolic homeostasis and mediates gut-brain communication. We hypothesized that vagus nerve dysfunction, induced by truncated vagotomy (VGX) or carotid artery occlusion (AO), would disrupt gut-brain communication and exacerbate metabolic dysregulation, neuroinflammation, and cognitive impairment. This study aimed to test the hypothesis in gerbils fed a high-fat diet. The gerbils were divided into four groups: AO with VGX (AO_VGX), AO without VGX (AO_NVGX), no AO with VGX (NAO_VGX), and no AO without VGX (NAO_NVGX). After 5 weeks on a high-fat diet, the neuronal cell death, neurological severity, hippocampal lipids and inflammation, energy/glucose metabolism, intestinal morphology, and fecal microbiome composition were assessed. AO and VGX increased the neuronal cell death and neurological severity scores associated with increased hippocampal lipid profiles and lipid peroxidation, as well as changes in the inflammatory cytokine expression and brain-derived neurotrophic factor (BDNF) levels. AO and VGX also increased the body weight, visceral fat mass, and insulin resistance and decreased the skeletal muscle mass. The intestinal morphology and microbiome composition were altered, with an increase in the abundance of Bifidobacterium and a decrease in Akkermansia and Ruminococcus. Microbial metagenome functions were also impacted, including glutamatergic synaptic activity, glycogen synthesis, and amino acid biosynthesis. Interestingly, the effects of VGX were not significantly additive with AO, suggesting that AO inhibited the vagus nerve activity, partly offsetting the effects of VGX. In conclusion, AO and VGX exacerbated the dysregulation of energy, glucose, and lipid metabolism, neuroinflammation, and memory deficits, potentially through the modulation of the gut-brain axis. Targeting the gut-brain axis by inhibiting vagus nerve suppression represents a potential therapeutic strategy for ischemic stroke.