Related Experiment Video
Updated: Aug 12, 2026

Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Proinflammatory cytokine expression contributes to brain injury provoked by chronic monocyte activation
A L Sirén1, R McCarron, L Wang
1Department of Neurology, The Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. siren@em.mpg.de
Background:
We have proposed that an increased interaction between monocyte/macrophages and blood vessel endothelium predisposes subjects to strokes. The effect of chronic monocyte activation on the development of cerebral infarcts was thus studied in rats after provocation of a modified local Swartzman reaction, in brain vasculature.
Materials And Methods:
Two weeks after an IV bolus of bacillus Calmette-Guérin (BCG), we studied spontaneous superoxide production, integrin expression, endothelial adhesion of monocytes and the neurological symptoms, brain histology, and cytokine immunoreactivity after a provocative dose of LPS (30-300 microg/rat i.c.v.).
Results:
Monocyte migration into the brain was stimulated by BCG priming. The incidence of paralysis and death in response to LPS was markedly increased in BCG-primed rats. Histological evaluation of the brains of neurologically impaired and moribund animals revealed intravascular thrombosis and pale and hemorrhagic infarcts. Infiltrates of leukocytes expressing immunoreactive IL-1:, IL-6, and TNF-alpha were found around blood vessels, cerebral ventricles, and meninges, and were accompanied by a profound microglial expression of IL1P, endothelial expression of IL-6, and expression of TNF-alpha and TNF-R 1 in glia and neurons of cortex and hippocampus. Treatment (2 x 100 microg/10 ,I, i.c.v.) with recombinant human (rh-)TNF 55kDa receptor completely prevented, and treatment with rh-IL- I receptor antagonist significantly decreased the incidence of paralysis and death in response to BCG + LPS. The improvement of neurological symptoms was accompanied by reduced histological damage and supppression of IL-1P/ expression in the brain tissue.
Conclusions:
The data demonstrate that chronic monocyte activation predisposes subjects to thrombosis and hemorrhage via an exaggerated release of proinflammatory cytokines.
Insights
Chronic monocyte activation primes rats for stroke by increasing brain inflammation and thrombosis. Blocking key inflammatory cytokines (TNF and IL-1) significantly reduced stroke incidence and severity in a rat model.
Area of Science:
- Neuroscience
- Immunology
- Vascular Biology
Background:
- Increased monocyte/macrophage interaction with endothelium is linked to stroke predisposition.
- Chronic monocyte activation's role in cerebral infarct development requires further investigation.
Purpose of the Study:
- To investigate the effect of chronic monocyte activation on cerebral infarct development in rats.
- To explore the role of specific cytokines in stroke pathogenesis.
Main Methods:
- Rats were primed with bacillus Calmette-Guérin (BCG) followed by lipopolysaccharide (LPS) challenge.
- Evaluated monocyte superoxide production, integrin expression, adhesion, neurological symptoms, brain histology, and cytokine profiles.
Main Results:
- BCG priming enhanced monocyte migration to the brain and increased paralysis/death post-LPS.
- Histology revealed thrombosis and infarcts, with elevated IL-1, IL-6, and TNF-alpha.
- Recombinant TNF receptor and IL-1 receptor antagonist treatments reduced stroke incidence and severity.
Conclusions:
- Chronic monocyte activation increases stroke risk through exaggerated proinflammatory cytokine release.
- Targeting IL-1 and TNF pathways may offer therapeutic strategies for stroke prevention.
Related Concept Videos
Inflammation
Differentiation of Common Myeloid Progenitor Cells
Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Acute Inflammation III: Local and Systemic Effects
Chronic Inflammation: Introduction
Bacterial Meningitis II: Pathophysiology

