Transient, early, female-specific increase in cortical glial fibrillary acidic protein distribution in the Syrian hamster model of mild peripheral COVID-19
Bibliographic record
Abstract
Abstract Background Mild-moderate respiratory COVID-19 is commonly associated with a range of neurological symptoms. The mechanisms linking this peripheral disease to cognitive symptoms are thought to include heightened circulating cytokines and other inflammatory mediators resulting in a leaky blood-brain barrier and increased neuroinflammation (i.e., inflammation taking place in the brain). This can lead to aberrant synaptic transmission and cognitive dysfunction. A key component of neuroinflammation is the reactivity of astrocytes, in a process termed ‘astrogliosis’, associated with altered morphology, proliferative capacity, gene expression, and function. Accumulating evidence suggests astrogliosis likely occurs in mild-moderate COVID-19; however, there has been limited investigation. In this study, we quantified changes to astrocytes in a Syrian hamster model of mild-moderate respiratory COVID-19. Methods We used an intranasal inoculation model to produce mild-moderate respiratory COVID-19 in 8–10-week-old male and female Syrian hamsters. We extracted brains at 1-, 3-, 5-, 7-, and 31-days post-inoculation and from uninfected controls, and immunolabelled brain sections with astrocyte- (GFAP and SOX9) and neuron-specific (NEUN) markers. We captured tiled confocal micrographs of entire brain sections and analyzed the resulting signals from five regions of interest: cortex, corpus callosum, hippocampus, third ventricle, and dorsal striatum. Results To systematically quantify cell-type-specific labelling for astrogliosis markers, we first developed an unbiased pipeline. We found a transient increase in GFAP signal density in female hamster, specifically in the cortex at 3 days post-inoculation. There were no corresponding changes noted in astrocyte (SOX9), neuron (NEUN) or total cell (Hoechst) numbers. Moreover, there were no changes in male hamsters at any timepoint in any region of interest. Conclusions Our findings provide the first spatiotemporal insight into astrogliosis in a hamster model of mild-moderate respiratory COVID-19. We identified a transient and sex-specific increase in GFAP signal density, indicative of astrogliosis. Our findings contribute to the literature surrounding sex differences in (neuro)immune responses and add to the growing body of COVID-19 literature, in which sex-specific outcomes are apparent in both human patient populations and rodent experimental models.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".