Dinh Quynh Nhu, Vinh Antony, Lo Cecilia, Wong Zhang David E, Figueiredo Galvao Hericka Bruna, Selvaraji Sharmelee, Kim Hyun Ah, Chrissobolis Sophocles, Arumugam Thiruma V, Drummond Grant R, Sobey Christopher G, De Silva T Michael
Centre for Cardiovascular Biology and Disease Research and La Trobe Institute for Molecular Sciences (LIMS), La Trobe University, Victoria, Australia.
Department of Microbiology, Anatomy, Physiology & Pharmacology, School of Agriculture, Biomedicine, Environment, La Trobe University, Victoria, Australia.
Brain Behav Immun Health. 2025 Jul 10;48:101059. doi: 10.1016/j.bbih.2025.101059. eCollection 2025 Oct.
Hypertension increases the risk for cognitive impairment and promotes vascular and renal inflammation. We tested if immune cell infiltration occurs in the brain during hypertension and if it is associated with cognitive impairment.
Male C57Bl/6 mice were administered vehicle, angiotensin II (0.7 mg/kg/d S.C.) or aldosterone (0.72 mg/kg/d S.C.) via osmotic minipumps. A subset of mice also received hydralazine (50 mg/kg) in their drinking water after minipump implantation. We measured systolic blood pressure, markers of inflammation, working memory and transcriptomic changes in the brain.
Administration of angiotensin II or aldosterone increased blood pressure and promoted blood-brain barrier dysfunction, leukocyte accumulation and impairment of working memory in mice. When co-administered with angiotensin II, hydralazine prevented the development of these changes. In a separate cohort of mice in which angiotensin II-induced changes were first established, intervention with hydralazine lowered blood pressure but did not reverse brain inflammation or cognitive impairment. Finally, angiotensin II infusion altered the transcriptomic profile of the whole brain, as well as specifically within the hippocampus, and co-treatment with hydralazine modulated these changes.
Experimental hypertension leads to brain inflammation and was associated with impaired working memory. Cognitive impairment that develops during hypertension can be inhibited, but not readily reversed, by anti-hypertensive therapy.
高血压会增加认知障碍风险，并促进血管和肾脏炎症。我们测试了高血压期间大脑中是否发生免疫细胞浸润以及它是否与认知障碍相关。
通过渗透微型泵给雄性C57Bl/6小鼠注射载体、血管紧张素II（0.7毫克/千克/天，皮下注射）或醛固酮（0.72毫克/千克/天，皮下注射）。一部分小鼠在植入微型泵后还在饮用水中摄入了肼屈嗪（50毫克/千克）。我们测量了收缩压、炎症标志物、工作记忆以及大脑中的转录组变化。
注射血管紧张素II或醛固酮会升高血压，并促进小鼠血脑屏障功能障碍、白细胞积聚和工作记忆受损。与血管紧张素II共同给药时，肼屈嗪可防止这些变化的发生。在另一组首先建立血管紧张素II诱导变化的小鼠中，用肼屈嗪进行干预可降低血压，但不能逆转脑部炎症或认知障碍。最后，注入血管紧张素II会改变整个大脑以及海马体内的转录组图谱，与肼屈嗪联合治疗可调节这些变化。
实验性高血压会导致脑部炎症，并与工作记忆受损相关。高血压期间出现的认知障碍可通过抗高血压治疗得到抑制，但不易逆转。
