{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:31:19Z","timestamp":1778599879738,"version":"3.51.4"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000034","name":"Institute of Neurosciences, Mental Health and Addiction","doi-asserted-by":"publisher","award":["174992"],"award-info":[{"award-number":["174992"]}],"id":[{"id":"10.13039\/501100000034","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022992","name":"Clinical Trials Fund, Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["167280"],"award-info":[{"award-number":["167280"]}],"id":[{"id":"10.13039\/100022992","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Ketone bodies, or ketones, are an alternative energy source and have several nonmetabolic signaling actions, such as inhibiting inflammation. Because of this, exogenous ketone supplementation has been used to help treat various diseases. \u03b2-hydroxybutyrate (\u03b2HB) is the major ketone body that has reduced neurological injury and brain edema in animal models of ischemic stroke and traumatic brain injury. However, the therapeutic potential of \u03b2HB in intracerebral hemorrhage (ICH) has not yet been determined. Here we investigated the effects of exogenous \u03b2HB treatment following ICH on inflammation, edema, injury size, and functional outcomes. To do this, we administered 250 mg\/kg of \u03b2HB (subcutaneously every 12 hours) starting 2 hours after collagenase-induced ICH in rats over 3 experiments. First, we observed that \u03b2HB-treated rats had significant reductions in transcript expression of pro-inflammatory markers <jats:italic>Il1b<\/jats:italic> (p = 0.0210), <jats:italic>Tnfa<\/jats:italic> (p = 0.0108), and <jats:italic>Mcp1<\/jats:italic> (p = 0.0473) 3 days post-ICH. Second, \u03b2HB significantly improved neurological deficits measured by the neurological deficit scale on day 3 (p = 0.0416) in another cohort of rats, despite no treatment effect on edema (p = 0.2110). To test whether the effects of acute \u03b2HB treatment (for 7 days post-ICH) were chronically sustained, the third experiment used serial behavioural testing which confirmed that \u03b2HB significantly improved neurological deficit scores (p = 0.0459) 3 days post-ICH. These effects were not sustained at 7, 14, and 28 days post-ICH (all p\u22650.1546). Similarly, \u03b2HB treatment did not yield differences in forelimb use asymmetry (all p&gt;0.45) or brain lesion volume (p = 0.3381), the primary endpoint of this study. Thus, our studies show that an acute \u03b2HB treatment post-ICH can provide some early signs of functional benefit without evidence of lasting effects or neuroprotection. However, it remains to be tested whether other \u03b2HB dosing regimens may favorably affect these and other neurological, behavioral, and biochemical parameters, particularly given the early signals of reduced striatal inflammation.<\/jats:p>","DOI":"10.1371\/journal.pone.0311778","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T18:53:27Z","timestamp":1733424807000},"page":"e0311778","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exogenous ketone therapy does not protect brain tissue after moderate-sized intracerebral hemorrhage despite signs of early neurological benefit"],"prefix":"10.1371","volume":"19","author":[{"given":"Noam H.","family":"Sander","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3488-1208","authenticated-orcid":true,"given":"Shubham","family":"Soni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassandra M.","family":"Wilkinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elmira","family":"Khiabani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7045-2884","authenticated-orcid":true,"given":"Jason R. 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