Exogenous ketone therapy does not protect brain tissue after moderate-sized intracerebral hemorrhage despite signs of early neurological benefit
Bibliographic record
Abstract
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. β-hydroxybutyrate (βHB) 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 βHB in intracerebral hemorrhage (ICH) has not yet been determined. Here we investigated the effects of exogenous βHB treatment following ICH on inflammation, edema, injury size, and functional outcomes. To do this, we administered 250 mg/kg of βHB (subcutaneously every 12 hours) starting 2 hours after collagenase-induced ICH in rats over 3 experiments. First, we observed that βHB-treated rats had significant reductions in transcript expression of pro-inflammatory markers Il1b (p = 0.0210), Tnfa (p = 0.0108), and Mcp1 (p = 0.0473) 3 days post-ICH. Second, βHB 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 βHB treatment (for 7 days post-ICH) were chronically sustained, the third experiment used serial behavioural testing which confirmed that βHB 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≥0.1546). Similarly, βHB treatment did not yield differences in forelimb use asymmetry (all p>0.45) or brain lesion volume (p = 0.3381), the primary endpoint of this study. Thus, our studies show that an acute βHB 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 βHB dosing regimens may favorably affect these and other neurological, behavioral, and biochemical parameters, particularly given the early signals of reduced striatal inflammation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".