ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2020
Subcutaneous administration of β-hydroxybutyrate improves learning and memory of sepsis surviving mice.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Time-restricted feeding protects against septic liver injury by reshaping gut microbiota and metabolite 3-hydroxybutyrate.Gut microbes · 2025Article
- Probiotic supplementation attenuated early-life chemotherapy-induced brain development impairment in mice.Frontiers in behavioral neuroscience · 2025Article
- SIRT3 is required for the protective function of ketogenic diet on neural inflammation and neuropathic pain.International journal of biological sciences · 2025Article
- The role of the peripheral system dysfunction in the pathogenesis of sepsis-associated encephalopathy.Frontiers in microbiology · 2024Review
- Microglial Activation: Key Players in Sepsis-Associated Encephalopathy.Brain sciences · 2023Review
- Astrocytic lactate dehydrogenase A regulates neuronal excitability and depressive-like behaviors through lactate homeostasis in mice.Nature communications · 2023Article
- Ketogenic Diet: An Effective Treatment Approach for Neurodegenerative Diseases.Current neuropharmacology · 2022Review
- Peripheral Transplantation of Mesenchymal Stem Cells at Sepsis Convalescence Improves Cognitive Function of Sepsis Surviving Mice.Oxidative medicine and cellular longevity · 2022Article
- (-)-Epicatechin Reduces Neuroinflammation, Protects Mitochondria Function, and Prevents Cognitive Impairment in Sepsis-Associated Encephalopathy.Oxidative medicine and cellular longevity · 2022Article
- Ketone Supplementation: Meeting the Needs of the Brain in an Energy Crisis.Frontiers in nutrition · 2021Review
- Potential Roles of Exercise-Induced Plasma Metabolites Linking Exercise to Health Benefits.Frontiers in physiology · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 β-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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.