Endotoxemia Prevents the Cerebral Inflammatory Wave Induced by Intraparenchymal Lipopolysaccharide Injection: Role of Glucocorticoids and CD14
Bibliographic record
Abstract
There is a robust and transient innate immune response in the brain during endotoxemia, which is associated with a cascade of NF-kappaB signaling events and transcriptional activation of genes that encode TNF-alpha and the LPS receptor CD14. The present study investigated whether circulating LPS has the ability to modulate the cerebral innate immune response caused by an intrastriatal (IS) injection of the endotoxin. We also tested the possibility that CD14 plays a role in these effects and male rats received an intracerebroventricular injection with an anti-CD14 before the IS LPS administration. The single LPS bolus into the striatum caused a strong and time-dependent transcriptional activation of TNF-alpha, IkappaBalpha, CD14, and monocyte chemoattractant protein-1 mRNA in microglial cells ipsilateral to the site of injection. Surprisingly, this wave of induced transcripts was essentially abolished by the systemic endotoxin pretreatment. Such anti-inflammatory properties of circulating LPS are mediated via plasma corticosterone, because exogenous corticoids mimicked while glucocorticoid receptor antagonist RU486 prevented the effects of systemic endotoxin challenge. Of interest is the partial involvement of CD14 in LPS-induced neuroinflammation; the anti-CD14 significantly abolished the microglial activity at day 3, but not at times earlier. The inflammatory response provoked by an acute intraparenchymal LPS bolus was not associated with convincing neurodegenerative processes. These data provide compelling evidence that systemic inflammation, through the increase in circulating glucocorticoids, has the ability to prevent the cerebral innate immune reaction triggered by an IS endotoxin injection. This study also further consolidates the existence of such system in the brain, which is finely regulated and its transient activation is not harmful for the neuronal elements.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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) | 0.000 | 0.000 |
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 teacher head, 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".