Abstract TMP52: Inactivated Microglia and Inhibition Neutrophil Infiltration Reduce Brain Injury Following Intracerebral Hemorrhage in Mice
Bibliographic record
Abstract
Introduction: Microglia become activated and monocytes become macrophages following intracerebral hemorrhage (ICH). They are often called “microglia/macrophage” since it is difficult to differentiate between them. The neutrophils also infiltrate into the injured brain after ICH. Those cells are capable of releasing numerous detrimental mediators. Hypothesis: The activation of microglia/macrophage and the infiltrated neutrophils promote brain injury after ICH and that inhibition both of them attenuates brain injury following ICH. Methods: 10-μl of autologous blood obtained from tail was introduced into the right striatum of adult male mice to produce ICH injury. We used transgenic CD11b thymidine kinase (CD11b-TK) mice where proliferating microglia/macrophage were removed by ganciclovir treatment. Functional grade purified anti-mouse Ly6G/Gr-1 antibodies were used to reduce the neutrophil infiltration. Groups of CD11b-TK mice were treated with ganciclovir and/or anti-mouse Ly6G/Gr-1 antibodies. These mice were killed at 3 days after ICH injury and brain sections were stained for various parameters. Results: ICH injury resulted in activation of microglia/macrophages through 1-7 days of ICH insult. The area of brain damage peaked at 2-3 days; the number of dying neurons peaked at 1-3 days, the number of infiltrated neutrophils peaked at 1-3 days, while the activation of microglia/macrophages peaked at days 3-4. These findings led us to choose day 3 for further studies. The activation of microglia/macrophage was significantly reduced in CD11b-TK transgenic mice with ganciclovir treatment after ICH. The numbers of infiltrated neutrophils were significantly reduced with anti-mouse Ly6G/Gr-1 antibodies treatment after ICH. Correspondingly, the area of brain damage and the extent of neuronal death were minimal in CD11b-TK mice with ganciclovir and anti-LyG6/Gr-1 antibodies treatment after ICH. Conclusions: Both activated microglia/macrophages and the infiltrated neutrophils after ICH promote brain injury. Thus inhibition of their activities reduces ICH brain injury. These results shed light on the advent of new medications for ICH patients, including microglia deactivators and the antibodies to alleviate neutrophil infiltration.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".