Erythropoietin and its antagonist regulate the hypoxic fictive breathing in newborn mice
Bibliographic record
Abstract
Erythropoietin (Epo) in adult mouse interacts with the major brainstem centers associated with respiration to enhance the ventilatory response to acute and chronic conditions of physiological hypoxia (e.g. as occuring at high altitude). However, whether Epo is as well implicated in the regulation of breathing in newborns remains unknown. To answer this question en bloc brainstem‐spinal cord preparations were obtained from mice at postnatal day 4 (P4). After time‐ (30, 60 or 90 min) and dose‐dependent (0, 25 or 250 U) incubation with or without Epo, en bloc preparations were superfused with artificial cerebrospinal fluid (aCSF) bubbled with normoxic or hypoxic gas mixtures. Subsequently, the electrophysiological fictive breathing produced by axons at the C4 ventral root was recorded. Our results show that upon hypoxic conditions Epo stimulates the neural hypoxic respiratory activity and improves the post hypoxic recovery. In addition, proof‐of‐concept experiments showed that soluble Epo receptor (sEpoR), the endogenous antagonist of Epo, dramatically decreases the neural hypoxic respiratory activity. These results imply that Epo and its endogenous antagonist in P4 mice are implicated in the modulation and maintenance of respiratory motor output during hypoxic and post‐hypoxic challenges. As Epo is a highly promising protective therapeutic agent for several brain diseases, these results suggest that Epo applications may be also relevant for neuronal‐related respiratory disorders in term and preterm neonates.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".