Abstract 3652: Sex Differences in CD200 and CD200R1 Expression in the Brain Following Experimental Stroke
Bibliographic record
Abstract
Background and Purpose Emerging data suggests that stroke-induced inflammation significantly contributes to neuronal injury and clinical outcome. Local inflammatory responses following cerebral ischemia have highlighted a pivotal role for the innate immune system in the brain’s response to injury, including activation of microglia and macrophages. Cell-surface receptors (e.g. CD200R1) on microglia and other myeloid-derived cells directly interact with specific endogenous ligands (e.g. CD200) expressed on neurons and act to suppress pro-inflammatory signaling by maintaining microglia in an “inactive state”. Recent studies investigating the imbalance of CD200-CD200R1 signaling in models of neurodegenerative disease support the hypothesis that this interaction may also be disrupted following stroke. We investigated the role of the immune inhibitory receptor CD200R1, and its ligand, CD200, after experimental stroke in both male and female mice. Methods Gonadally intact male and female C57BL/6 mice were subjected to middle cerebral artery occlusion by reversible right MCA occlusion for 90min followed by 6h of reperfusion. Brains were harvested and processed for RNA and protein. mRNA and protein were analyzed for CD200 and CD200R1 expression using qPCR and Western blotting respectively in both stroke and sham mice. Immunohistochemistry was performed to identify the cellular source of CD200 and CD200R1 expression. Results At 6h post-reperfusion, decreased CD200 gene expression was seen in both sexes compared to sham. Western blot analysis demonstrated that CD200 was significantly decreased in males compared to females after stroke. CD200R1 gene levels were also downregulated in males compared to sham, however expression levels in females were increased after stroke. A relative 4-fold increase in CD200R1 protein levels was seen in stroke males compared to sham, in contrast CD200R1 expression in females decreased following stroke. Conclusions Early in the post-ischemic period, a marked difference between males and females in both CD200 and CD200R1 expression was seen, suggesting sex-dependent modulation of the stroke-induced inflammatory response. The decrease in CD200 ligand expression in males following stroke would be expected to lead to decreased CD200R1 activation, freeing microglial inhibition, thereby promoting a pro-inflammatory response. The increase in CD200R1 expression following stroke in males may act as a compensatory mechanism, potentially serving to enhance CD200-CD200R1 interactions between neurons and myeloid cells and thus suppress inflammation. These results provide a novel explanation for the larger cerebral infarcts seen in males, by a mechanism whereby stroke-induced disruption of the immunosuppressant interaction between CD200 and CD200R1 leads to worse outcome.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".