A unique cerebellar pattern of microglia activation in a mouse model of encephalopathy of prematurity
Bibliographic record
Abstract
Abstract Preterm infants often show pathologies of the cerebellum, which are associated with impaired motor performance, lower IQ and poor language skills at school ages. Because 1 in 10 babies is born preterm cerebellar injury is a significant clinical problem. The causes of cerebellar damage are yet to be fully explained. Herein, we tested the hypothesis that perinatal inflammatory stimuli may play a key role in cerebellar injury of preterm infants. We undertook our studies in an established mouse model of inflammation-induced encephalopathy of prematurity driven by systemic administration of the prototypic pro-inflammatory cytokine interleukin-1β (IL-1β). Inflammation is induced between postnatal day (P) 1 to day 5, timing equivalent to the last trimester for brain development in humans the period of vulnerability to preterm birth related brain injury. We investigated acute and long-term consequences for the cerebellum on brain volume expansion, oligodendroglial maturation, myelin levels and the microglial transcriptome. Perinatal inflammation induced global mouse brain volume reductions, including specific grey and white matter volume reductions in cerebellar lobules I and II (5% FDR) in IL-1β versus control treated mice from P15 onwards. Oligodendroglia damage preceded the MRI-detectable volume changes, as evidenced by a reduced proliferation of OLIG2+ cells at P10 and reduced levels of the myelin proteins MOG, MBP and MAG at P10 and P15. Increased density of Iba1+ cerebellar microglia was observed at P5 and P45, with evidence for increased microglial proliferation at P5 and P10. Comparison of the transcriptome of microglia isolated from P5 cerebelli and cerebrum revealed significant enrichment of pro-inflammatory markers in microglia from both regions, but in the cerebellum microglia displayed a unique type I interferon signalling dysregulation. Collectively, these data suggest that in our model that systemic inflammation causes chronic activation of microglia and maldevelopment of cerebellum that includes myelin deficits which is driven in the cerebellum by type I interferon signalling. Future protective strategies for preterm infants should consider sustained type I interferon signalling driven cerebellar inflammation as an important target.
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".