Additional file 4 of Reduced microglia activation following metformin administration or microglia ablation is sufficient to prevent functional deficits in a mouse model of neonatal stroke
Bibliographic record
Abstract
Additional file 4: Figure S4. Dose-dependentmicroglia ablation is seen following one week of daily injections of Plexxikon.A Experimental timeline following PLX 5622 administration (vehicle control,10ug/g or 50ug/g) from P8 to P15. Immunohistochemistry (IHC) or the neurosphereassay (NS) was performed on P15. B No differences in pup weight were recordedacross treatment groups. C Representative image of microglia (Iba1+, red) atP15 in the cortex in Sham mice (20x magnification). D Representative image ofmicroglia (Iba1+, red) at P15 in the cortex in mice that received 10ug PLX fromP8 to 15 (20x magnification). E Representative image of microglia (Iba1+, red)at P15 in the cortex in mice that received 50ug PLX from P8 to 15 (20xmagnification). F Quantification of the number microglia (Iba1+ cells/area) inthe cortex, reported as fold change. Microglia are significantly depleted with10ug/g PLX (1.00±0.11-fold change of Iba1+ cells in vehicle-treated mice vs.0.52±0.03-fold change Iba1+ cells in 10ug/g PLX-treated mice) (p=0.008) and50ug/g PLX (1.00±0.11-fold change of Iba1+ cells in vehicle-treated mice vs.0.18± 0.05-fold change of Iba1+ cells in 50ug/g PLX-treated mice (p=0.0004).PLX at 50ug/g results in a significantly greater loss of Iba1+ cells comparedto 10ug/g (0.52±0.03-fold change Iba1+ cells in 10ug/g PLX-treated mice vs.0.18±0.05-fold change of Iba1+ cells in 50ug/g PLX-treated mice) (p=0.033).Average number of Iba1+cells/unit area: Vehicle=67.17±7.21; 10ug/gPLX=35.28±2.29; 50ug/g PLX=12.42±3.2. G Representative image of microglia(Iba1+, red) at P15 in the striatum in Sham mice (20x magnification). HRepresentative image of microglia (Iba1+, red) at P15 in the striatum in micethat received 10ug PLX from P8 to 15 (20x magnification). I Representativeimage of microglia (Iba1+, red) at P15 in the striatum in mice that received50ug PLX from P8 to 15 (20x magnification). J Quantification of the numbermicroglia (Iba1+ cells/area) in the striatum, reported as fold change.Microglia are not depleted with PLX at 10ug/g (1.00± 0.08-fold change of Iba1+cells in vehicle-treated mice vs. 0.77±0.08-fold change Iba1+ cells in 10ug/gPLX-treated mice) (p=0.4514) but are significantly reduced with 50ug/g PLX(1.00± 0.08-fold change of Iba1+ cells in vehicle-treated mice vs.0.25±0.04-fold change of Iba1+ cells area in 50ug/g PLX-treated mice vs.vehicle (p=0.003). PLX at 50ug/g results in a significantly greater loss ofIba1+ cells compared to 10ug/g (0.77±0.08-fold change Iba1+ cells in 10ug/gPLX-treated mice vs. 0.25±0.04-fold change of Iba1+ cells in 50ug/g PLX-treatedmice) (p=0.0034). Average number of Iba1+cells/unit area: Vehicle = 32.19±2.65;10ug/g = 28.00 ± 2.65; 50ug/g PLX = 9.83±1.36. K Representative image ofmicroglia (Iba1+, red) at P15 in the SEZ in Sham mice (20x magnification). LRepresentative image of microglia (Iba1+, red) at P15 in the SEZ in mice thatreceived 10ug PLX from P8 to 15 (20x magnification). M Representative image ofmicroglia (Iba1+, red) at P15 in the SEZ in mice that received 50ug PLX from P8to 15 (20x magnification). N Quantification of the number microglia (Iba1+cells/ area) in the SEZ, reported as fold change. Microglia are significantlydepleted with 10ug/g PLX (1.00± 0.04-fold change of Iba1+ cells invehicle-treated mice vs. 0.55±0.03-fold change Iba1+ cells in 10ug/gPLX-treated mice) (p=0.0002) and 50ug/g PLX (0.31±0.01-fold change of Iba1+cells in vehicle-treated mice vs. 0.18±0.05-fold change of Iba1+ cells in50ug/g PLX-treated mice (p=0.004). PLX at 50ug/g results in a significantlygreater loss of Iba1+ cells compared to 10ug/g (0.55±0.03-fold change Iba1+cells in 10ug/g PLX-treated mice vs. 0.31±0.01fold change of Iba1+ cells in50ug/g PLX-treated mice) (p=0.0038). Average number of Iba1+cells/unit area:Vehicle=20.03±0.87; 10ug/g PLX=11.11±0.68; 50ug/g PLX=6.19±0.10±1.36. O Nodifference in neurosphere numbers were observed across treatment groups(p=0.39). Average number of neurospheres: Vehicle = 6.33±0.96; PLX: 7.33±0.42. n=3 mice per group. Data presented as mean ± SEM. Unit area (cortex, striatum):3x0.105 mm2. Unit area (SEZ): 3x0.045mm2. Statistics: (B) Two-way ANOVA; (C-E)One-way ANOVA. (O) Unpaired t-test. *p<0.050.
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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 | 0.002 | 0.015 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.876 | 0.132 |
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".