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Subcutaneous administration of ß-hydroxybutyrate improves learning and memory of sepsis surviving mice.
Wang, Xueqin; Song, Yaying; Chen, Jie; Zhang, Shuibing; Le, Yuan; Xie, Zhongcong; Ouyang, Wen; Tong, Jianbin.
Afiliación
  • Wang X; Center for Experimental Medicine, Third Xiangya Hospital, Central South University, 138th Tongzipo Road, Yuelu District, Changsha, 410013, People's Republic of China.
  • Song Y; Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China.
  • Chen J; Center for Experimental Medicine, Third Xiangya Hospital, Central South University, 138th Tongzipo Road, Yuelu District, Changsha, 410013, People's Republic of China.
  • Zhang S; Department of Anesthesiology, Third Xiangya Hospital, Central South University, 138th Tongzipo Road, Yuelu District, Changsha, 410013, People's Republic of China.
  • Le Y; Department of Anesthesiology, Third Xiangya Hospital, Central South University, 138th Tongzipo Road, Yuelu District, Changsha, 410013, People's Republic of China.
  • Xie Z; Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129-2060, USA.
  • Ouyang W; Department of Anesthesiology, Third Xiangya Hospital, Central South University, 138th Tongzipo Road, Yuelu District, Changsha, 410013, People's Republic of China. ouyangwen133@vip.sina.com.
  • Tong J; Center for Experimental Medicine, Third Xiangya Hospital, Central South University, 138th Tongzipo Road, Yuelu District, Changsha, 410013, People's Republic of China. jianbintong@csu.edu.cn.
Neurotherapeutics ; 17(2): 616-626, 2020 04.
Article en En | MEDLINE | ID: mdl-31853744
Post-sepsis cognitive impairment is one of the major sequelae in sepsis survivors. Its prevention remains clinically challenging. Here we tested the effects and underlying mechanisms of exogenous ß-hydroxybutyrate (BHB) on post-sepsis cognitive impairment. We found that subcutaneous administration of BHB increased survival and body weight recovery of sepsis mice and improved learning and memory of sepsis surviving mice in a cecal ligation and perforation-induced sepsis model. Additionally, the improvement of learning and memory of sepsis surviving mice was still detected even if BHB was administrated at the late stage of sepsis. In contrast, glucose solution did not show similar effects. Mechanistically, subcutaneous administration of BHB increased the BHB level of hippocampus, and limited neuroinflammation and neuroplasticity damage in sepsis mice. Intracerebroventricular administration of BHB also alleviated neuroinflammation and cognitive impairment of sepsis surviving mice. In the coculture of neurons, astrocytes, and BV2 cells (a microglial cell line), knocking down the expression of microglial HCA2 (BHB receptor) via a specific shRNA reduced the protection of BHB to lipopolysaccharide-induced inflammatory response and neuron damage more significantly than knocking down neuronal MCT2 (BHB transporter). These data showed that (1) BHB was a potential pharmacological adjunct treatment for prevention of post-sepsis cognitive impairment and (2) inhibiting neuroinflammation via HCA2 was an important mechanism.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sepsis / Ácido 3-Hidroxibutírico / Disfunción Cognitiva / Aprendizaje / Memoria Límite: Animals Idioma: En Revista: Neurotherapeutics Asunto de la revista: NEUROLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sepsis / Ácido 3-Hidroxibutírico / Disfunción Cognitiva / Aprendizaje / Memoria Límite: Animals Idioma: En Revista: Neurotherapeutics Asunto de la revista: NEUROLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos