ISDN2014_0340: <i>In vitro</i> pro‐inflammatory phenotype of fetal brain microglia is potentiated by an <i>in vivo</i> pre‐exposure to inflammation: A prospective study in ovine fetus near term
Bibliographic record
Abstract
Neuroinflammation in utero may result in life-long neurological deficits with microglia thought to play a key role. Double-hit experimental models of neuroinflammation are needed. We aimed to develop an in vivo – in vitro exposure model of neuroinflammation. Near-term ovine fetuses were surgically instrumented with arterial and venous catheters. At 0.89 gestation (∼35 weeks in humans), animals received either lipopolysaccharide (LPS group, n = 12) or saline (Control, n = 9) intravenously on experimental days 1 and 2. Fetal arterial blood samples were taken at baseline and selected time points post LPS for plasma cytokines ELISA (IL-1beta and IL-6). At 54 hours, the animals were euthanized. Brains from instrumented fetuses and twins (controls) were perfusion-fixed for immunohistochemical analysis of regional microglia counts. In addition, two cell cultures were derived from brains of in vivo LPS exposed group and six cultures from brains of in vivo controls. Microglia were cultured for 6 h with or without LPS. Microglia purity was verified immunocytochemically and by flow cytometry. Cell conditioned media were collected and IL-1beta was measured (ELISA). Results were considered significant if P < 0.05. In vivo, IL-6, but not IL-1beta, peaked at 3 hours and declined to basal levels at 24 hours after the first LPS injection, with no further increase in IL-6 after the second LPS injection. LPS group showed higher regional microglia counts vs. controls. In vitro, at baseline, microglia secreted more IL-1beta in the in vivo LPS group than in Controls. LPS re-exposure further increased IL-1beta versus baseline. The relative IL-1beta increase was ∼4.6-fold in both cases. Inflammatory microglial phenotype acquired during in vivo exposure to LPS is sustained and potentiated in vitro upon re-exposure to LPS. This model allows studying mechanisms of fetal neuroinflammation in utero and in vitro to identify potential therapeutic targets for early postnatal intervention.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".