Abstract W P205: Specific Deficiency of Brain ABCA1 Increases Inflammation and White Matter Damage and Worsens Functional Outcome After Stroke
Bibliographic record
Abstract
Background: ATP-binding cassette transporter A1 (ABCA1) plays a critical role in HDL-cholesterol production and has been identified as a potent anti-inflammatory molecule in macrophages and other immune cells. However, direct experimental support of this hypothesis in cerebral ischemia is lacking. Using specific deficiency of brain ABCA1 mice, we therefore tested whether ABCA1 plays a role in neuro-inflammation and white matter damage after stroke. Methods: Adult male brain ABCA1 knockout control (floxed, ABCA1 fl/fl ) and brain ABCA1 knockout (floxed, nestin-Cre positive, ABCA1 -B/-B ) mice were subjected to permanent extraluminal distal middle cerebral artery occlusion (dMCAo) by transcranial ligation of distal MCA with a 10-0 filament. Animals were sacrificed 7 days after MCAo. A battery of functional outcomes, infarct volume, and immunostaining for analysis of inflammation and white matter damage were performed. Results: There is no significant difference in blood level of total cholesterol, triglyceride and HDL before and after MCAo between ABCA1 -B/-B and ABCA1 fl/fl mice. However, ABCA1 -B/-B mice showed: 1) increased infarct volume (21.67%±2.95%, n=14, p=0.022) compared with ABCA1 fl/fl (11.57%±1.58%, n=9); 2) decreased functional outcome evaluated by the adhesive removal and basket tests performed at 1, 3 and 7 days after MCAo (p<0.05); 3) increased inflammation in the ischemic brain, including: (a) decreased the number of CD163 (M2 macrophage marker, anti-inflammatory) positive cells, but an increased the ratio of ED1 (M1 macrophage marker, pro-inflammatory)/CD163 positive cells; ( b ) increased matrix metalloproteinase-9 (MMP-9) expression measured by immunostaining; ( c ) increased number of NFkB positive cells; 4) increased white matter damage: decreased density of Luxol Fast Blue (myelin marker, p<0.01) and Bielshowsky silver (axon marker, p<0.05) compared to ABCA1fl/fl mice. Conclusions: Specific deficiency of brain ABCA1 increases inflammation and white matter damage in the ischemic brain, which may play important roles in increasing infarct volume and decreasing functional outcome after stroke. These data indicate that ABCA1 plays an important role in inhibiting neuro-inflammation in the ischemic brain after stroke.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.010 | 0.002 |
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".