{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:27:52Z","timestamp":1785770872150,"version":"3.56.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Bacterial infection of the central nervous system (CNS) poses a clinical challenge and is a leading cause of neurological disorders in cattle. Human studies have demonstrated an increase in cerebrospinal fluid (CSF) L-lactate levels in bacterial meningitis. The aims of this study were to establish a Reference Interval (RI) for L-lactate in bovine CSF and assess its potential as a biomarker for detecting infectious-inflammatory disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CSF L-lactate was measured in the field using a commercially available lactate monitor. The RI for CSF L-lactate was calculated on healthy animals; univariate and receiver operating characteristic (ROC) analyses were performed to disclose an association between CSF L-lactate levels and interpretation of CSF in sick animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty-seven healthy cattle and 86 sick cattle with either CNS infectious-inflammatory disorders (47\/86) or CNS disorders of other etiology (39\/86) were included in this prospective study. The RI for CSF L-lactate was 1.1\u20132.4\u2009mmol\/L. The concentration was higher in the cattle with neutrophilic pleocytosis and the area under the ROC curve was 0.92 compared to other animals. Based on a cut-off of 3.15\u2009mmol\/L, CSF L-lactate had diagnostic sensitivity and specificity for neutrophilic pleocytosis of 93 and 80%, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This is the first study to determine a RI for CSF L-lactate in cattle. Elevated CSF L-lactate levels indicated neutrophilic pleocytosis, which is often manifested in acute bacterial infection. The present findings may aid in diagnosis and correct use of antimicrobial drugs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fvets.2024.1466920","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T04:10:15Z","timestamp":1728447015000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Cerebrospinal fluid L-lactate as a diagnostic marker for infectious-inflammatory disorders in the central nervous system of cattle"],"prefix":"10.3389","volume":"11","author":[{"given":"Sara","family":"Ferrini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Cagnotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugo","family":"Ala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Avilii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Bellino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Biasibetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliano","family":"Borriello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiano","family":"Corona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Di Muro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Iamone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Iulini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Pezzolato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Bozzetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"D\u2019Angelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1177\/1040638719854788","article-title":"Central nervous system diseases of cattle in Georgia, 2001\u20132017","volume":"31","author":"Clarke","year":"2019","journal-title":"J Vet Diagn Invest"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1111\/jvim.16664","article-title":"A novel machine learning-based web application for field identification of infectious and inflammatory disorders of the central nervous system in cattle","volume":"37","author":"Ferrini","year":"2023","journal-title":"J Vet Intern Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.cvfa.2004.03.002","article-title":"Bacterial meningitis and encephalitis in ruminants","volume":"20","author":"Fecteau","year":"2004","journal-title":"Vet Clin Nth Amer Food Anim Pract"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.cvfa.2004.02.004","article-title":"Diagnostic techniques and clinicopathologic findings in ruminant neurologic disease","volume":"20","author":"Scott","year":"2004","journal-title":"Vet Clin Nth Amer Food Anim Pract"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1111\/j.1939-165X.2008.00094.x","article-title":"Cerebrospinal fluid findings in cattle with central nervous system disorders: a retrospective study of 102 cases (1990-2008)","volume":"38","author":"Stokol","year":"2009","journal-title":"Vet Clin Pathol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1007\/s11259-022-09949-w","article-title":"Feasibility of 16S rRNA sequencing for cerebrospinal fluid microbiome analysis in cattle with neurological disorders: a pilot study","volume":"47","author":"Ferrini","year":"2023","journal-title":"Vet Res Comm"},{"key":"ref7","first-page":"187","article-title":"CSF in acute and chronic infectious diseases","volume-title":"Handbook of clinical neurology","author":"Benninger","year":"2017"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1865-1380-7-14","article-title":"Cerebrospinal fluid lactate level as a diagnostic biomarker for bacterial meningitis in children","volume":"7","author":"Mekitarian Filho","year":"2014","journal-title":"Int J Emerg Med"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"R240","DOI":"10.1186\/cc9395","article-title":"Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: a systemic review and meta-analysis","volume":"14","author":"Huy","year":"2010","journal-title":"Crit Care"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1086\/520184","article-title":"Predictive value of cerebrospinal fluid (CSF) lactate level versus CSF\/blood glucose ratio for the diagnosis of bacterial meningitis following neurosurgery","volume":"29","author":"Leib","year":"1999","journal-title":"Clin Infect Dis"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.jinf.2011.02.010","article-title":"Diagnostic accuracy of cerebrospinal fluid lactate for differentiating bacterial meningitis from aseptic meningitis: a meta-analysis","volume":"62","author":"Sakushima","year":"2011","journal-title":"J Inf"},{"key":"ref12","first-page":"82","article-title":"Comparison between cerebrospinal fluid and serum lactate concentrations in neurologic dogs with and without structural intracranial disease","author":"Benedicenti","year":"2018","journal-title":"Can J Vet Res"},{"key":"ref13","first-page":"297","article-title":"Evaluation of cerebrospinal fluid lactate and plasma lactate concentrations in anesthetized dogs with and without intracranial disease","volume":"77","author":"Cainnes","year":"2013","journal-title":"Can J Vet Res"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1111\/vcp.12918","article-title":"Association between cerebrospinal fluid lactate concentration and central nervous system disease in dogs","volume":"49","author":"Fitz","year":"2020","journal-title":"Vet Clin Pathol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"2701","DOI":"10.1111\/jvim.15606","article-title":"Cerebrospinal fluid lactate in dogs with inflammatory central nervous system disorders","volume":"33","author":"Mariani","year":"2019","journal-title":"J Vet Intern Med"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"105395","DOI":"10.1016\/j.tvjl.2019.105395","article-title":"Cerebrospinal fluid and blood lactate concentrations as prognostic biomarkers in dogs with meningoencephalitis of unknown origin","volume":"254","author":"Portero","year":"2019","journal-title":"Vet J"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"2562","DOI":"10.1111\/jvim.15953","article-title":"Cerebrospinal fluid lactate concentrations in dogs with seizure disorders","volume":"34","author":"Mariani","year":"2020","journal-title":"J Vet Intern Med"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1111\/vcp.12567","article-title":"Validation of a portable monitor for assessment of cerebrospinal fluid lactate in dogs","volume":"47","author":"Nye","year":"2018","journal-title":"Vet Clin Pathol"},{"key":"ref19","first-page":"146","article-title":"L-lactate in cerebrospinal fluid can be used as a biomarker of encephalitis in cattle","volume":"84","author":"Curti","year":"2020","journal-title":"Can J Vet Res"},{"key":"ref20","first-page":"48","article-title":"Classification of neurological diseases: Vitamin D","volume-title":"Small animal neurology, an illustrated text","author":"Jaggy","year":"2010"},{"key":"ref21","first-page":"55","article-title":"Ancillary diagnostic aids","volume-title":"Large animal neurology","author":"Mayhew","year":"2022"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1136\/vr.164.16.491","article-title":"Analysis of cerebrospinal fluid from 20 calves after storage for 24 hours","volume":"164","author":"D\u2019Angelo","year":"2009","journal-title":"Vet Rec"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1111\/vcp.12006","article-title":"ASVCP reference interval guidelines: determination of de novo reference intervals in veterinary species and other related topics","volume":"41","author":"Friedrichs","year":"2012","journal-title":"Vet Clin Pathol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1001\/archneur.1967.00470230044005","article-title":"Independence of blood and cerebrospinal fluid lactate","volume":"16","author":"Posner","year":"1967","journal-title":"Arch Neurol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nrn.2018.19","article-title":"Lactate in the brain: from metabolic end-product to signalling molecule","volume":"19","author":"Magistretti","year":"2018","journal-title":"Nat Rev Neurosci"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"736","DOI":"10.3171\/jns.1988.69.5.0736","article-title":"Production and clearance of lactate from brain tissue, cerebrospinal fluid, and serum following experimental brain injury","volume":"69","author":"Inao","year":"1988","journal-title":"J Neurosurg"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"165542","DOI":"10.1016\/j.bbadis.2019.165542","article-title":"Glycolysis dependent lactate formation in neutrophils: a metabolic link between NOX-dependent and independent NETosis","volume":"1865","author":"Awasthi","year":"2019","journal-title":"Biochim Biophys Acta Mol basis Dis"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1002\/bies.201300084","article-title":"The Warburg effect then and now: from cancer to inflammatory diseases","volume":"35","author":"Palsson-Mcdermott","year":"2013","journal-title":"BioEssays"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"808799","DOI":"10.3389\/fimmu.2021.808799","article-title":"Role of lactate in inflammatory processes: friend or foe","volume":"12","author":"Manosalva","year":"2022","journal-title":"Front Immunol"},{"key":"ref30","first-page":"341","article-title":"Lactate and glucose in cerebrospinal fluid heavily contaminated with blood","volume":"45","author":"Begovac","year":"1991","journal-title":"Acta Med Croatica"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"866","DOI":"10.2460\/javma.1997.211.07.866","article-title":"Effects of iatrogenic blood contamination on results of cerebrospinal fluid analysis in clinically normal dogs and dogs with neurologic disease","volume":"211","author":"Hurtt","year":"1997","journal-title":"J Am Vet Med Ass"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1152\/ajplegacy.1962.202.6.1049","article-title":"Hyperthermia, lactic acid infusion, and the composition of arterial blood and cerebrospinal fluid","volume":"202","author":"Alexander","year":"1962","journal-title":"Am J Phys"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1136\/practneurol-2019-002191","article-title":"CSF lactate","volume":"20","author":"Baheerathan","year":"2020","journal-title":"Pract Neurol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1016\/j.cca.2012.06.018","article-title":"The clinical diagnostic significance of cerebrospinal fluid d-lactate for bacterial meningitis","volume":"413","author":"Chen","year":"2012","journal-title":"Clin Chim Acta"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2024.1466920\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T04:10:21Z","timestamp":1728447021000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2024.1466920\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,9]]},"references-count":34,"alternative-id":["10.3389\/fvets.2024.1466920"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2024.1466920","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,9]]},"article-number":"1466920"}}