{"title":"A budget for brain metabolic water production by glucose catabolism during rest, rises in activity and sleep.","authors":"Gerald A Dienel, Martin Lauritzen","doi":"10.1186/s12987-025-00647-8","DOIUrl":null,"url":null,"abstract":"<p><p>Maintaining brain fluid homeostasis is of critical importance for creating a stable environment conducive to optimal neuronal functioning, nutrient distribution, and waste product removal. In this study, we employed previously published data on brain oxygen and glucose consumption in awake rodents or humans to quantify the metabolic water production associated with distinct pathways of glucose metabolism. It is predicted that neuronal mitochondria are the primary source of metabolic water at rest, resulting in a continuous efflux into the cytosol, interstitial fluid, and cerebrospinal fluid. Net metabolic water production is predicted to be reduced by increases in activity due to a shift in metabolism from glucose oxidation to include glycolysis in neurons and ATP hydrolysis by the major cation pumps, which involves water consumption (ATP + H<sub>2</sub>O → ADP + Pi). In comparison, glycogenolysis, which occurs concurrently with the activation of astrocytes, potentially represents a major but previously unidentified contributor to metabolic water. Metabolic water production is dependent on the state of the brain, with a reduction of 30-40% occurring during deep sleep. Our estimates indicate that metabolic water functions as a conduit for interstitial fluid production within the brain, enabling flexible and efficient distribution of fluid that flows seamlessly from the parenchyma to the subarachnoid space and lymphatic vessels to facilitate the removal of brain waste, independent of the glymphatic system.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"44"},"PeriodicalIF":5.9000,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057207/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Fluids and Barriers of the CNS","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12987-025-00647-8","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Maintaining brain fluid homeostasis is of critical importance for creating a stable environment conducive to optimal neuronal functioning, nutrient distribution, and waste product removal. In this study, we employed previously published data on brain oxygen and glucose consumption in awake rodents or humans to quantify the metabolic water production associated with distinct pathways of glucose metabolism. It is predicted that neuronal mitochondria are the primary source of metabolic water at rest, resulting in a continuous efflux into the cytosol, interstitial fluid, and cerebrospinal fluid. Net metabolic water production is predicted to be reduced by increases in activity due to a shift in metabolism from glucose oxidation to include glycolysis in neurons and ATP hydrolysis by the major cation pumps, which involves water consumption (ATP + H2O → ADP + Pi). In comparison, glycogenolysis, which occurs concurrently with the activation of astrocytes, potentially represents a major but previously unidentified contributor to metabolic water. Metabolic water production is dependent on the state of the brain, with a reduction of 30-40% occurring during deep sleep. Our estimates indicate that metabolic water functions as a conduit for interstitial fluid production within the brain, enabling flexible and efficient distribution of fluid that flows seamlessly from the parenchyma to the subarachnoid space and lymphatic vessels to facilitate the removal of brain waste, independent of the glymphatic system.
期刊介绍:
"Fluids and Barriers of the CNS" is a scholarly open access journal that specializes in the intricate world of the central nervous system's fluids and barriers, which are pivotal for the health and well-being of the human body. This journal is a peer-reviewed platform that welcomes research manuscripts exploring the full spectrum of CNS fluids and barriers, with a particular focus on their roles in both health and disease.
At the heart of this journal's interest is the cerebrospinal fluid (CSF), a vital fluid that circulates within the brain and spinal cord, playing a multifaceted role in the normal functioning of the brain and in various neurological conditions. The journal delves into the composition, circulation, and absorption of CSF, as well as its relationship with the parenchymal interstitial fluid and the neurovascular unit at the blood-brain barrier (BBB).