Inflammatory Mediators of Cerebral Endothelium: A Role in Ischemic Brain Inflammation
Bibliographic record
Abstract
Brain inflammation has been implicated in the development of brain edema and secondary brain damage in ischemia and trauma. Adhesion molecules, cytokines and leukocyte chemoattractants released/presented at the site of blood‐brain barrier (BBB) play an important role in mobilizing peripheral inflammatory cells into the brain. Cerebral endothelial cells (CEC) are actively engaged in processes of microvascular stasis and leukocyte infiltration by producing a plethora of pro‐inflammatory mediators. When challenged by external stimuli including cytokines and hypoxia, CEC have been shown to release/express various products of arachidonic acid cascade with both vasoactive and pro‐inflammatory properties, including prostaglandins, leukotrienes, and platelet‐activating factor (PAF). These metabolites induce platelet and neutrophil activation and adhesion, changes in local cerebral blood flow and blood rheology, and increases in BBB permeability. Ischemic CEC have also been shown to express and release bioactive inflammatory cytokines and chemokines, including IL‐Iβ, IL‐8 and MCP‐1. Many of these mediators and ischemia in vitro and in vivo have been shown to up‐regulate the expression of both selectin and Ig‐families of adhesion molecules in CEC and to facilitate leukocyte adhesion and transmigration into the brain. Collectively, these studies demonstrate a pivotal role of CEC in initiating and regulating inflammatory responses in cerebral ischemia. Summary Inflammatory genes/mediators are involved in molecular/biochemical cascades determining stroke outcome. Cerebral endothelial cells, targeted by inflammatory mediators produced in ischemic brain, undergo pro‐inflammatory activation by expressing/secreting various inflammatory mediators, thus becoming a source of inflammation themselves. A unique position of the cerebral endothelial cells at the interface between blood and brain establishes their role as principal regulators of peripheral inflammatory cell recruitment into the brain during stroke. Cerebral endothelial cells also exhibit ability to regulate vasomotor responses of brain microcirculation and the permeability of the BBB, both important components of inflammation. Therefore, approaches to attenuate consequences of stroke must take into consideration cerebral endothelial cells as an easily accessible target to interfere with the ischemic brain inflammation.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| 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".