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Entry of monocytes into the brain after injection of Corynebacterium parvum
L Cheng1, R J Allore, P M Richardson
1Division of Neurosurgery, Montreal General Hospital, Quebec, Canada.
Abstract:
The receptiveness of the brain to monocyte infiltration was studied in rats that had been injected intracerebrally with Corynebacterium parvum. At 0-17 days after intracerebral injection and 18 h after intravenous injection of diI-labeled isogenous mononuclear cells, host rats were sacrificed and cells from the vicinity of the injection site and from the contralateral cerebral hemisphere were dissociated and analyzed by flow cytometry. In rats sacrificed 4-11 days postinjection of C. parvum, diI-labeled mononuclear cells were detected in cell preparations from the hemisphere ipsilateral and, to a lesser extent, contralateral to the injection site. No extravasation of cells from the blood to the brain was detected in rats injected intracerebrally with saline. By immunohistochemistry, many macrophages were detected in the hemisphere ipsilateral to injection of C. parvum. In additional experiments, the dissociated CNS cell population was labeled with OX-42 antibodies to the type 3 complement receptor, which is present on monocytes but not lymphocytes. Some cells in the brain were labeled with both diI and OX-42 and therefore were identified as monocytes that had entered the brain from the blood. In conclusion, monocytes can home to both sides of the brain after unilateral injection of a strong inflammatory agent but monocyte infiltration into the brain is delayed in comparison to monocyte inflammatory responses that have been reported in nonneural tissues.
Insights
Monocytes can infiltrate both sides of the brain following inflammatory agent injection. However, this brain monocyte infiltration is slower than in other tissues.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Immunology
Background:
- The brain's immune privilege is challenged by inflammatory stimuli.
- Understanding monocyte infiltration is crucial for neuroinflammatory diseases.
Purpose of the Study:
- To investigate the brain's receptiveness to monocyte infiltration after inflammatory stimulation.
- To track the migration of monocytes into the central nervous system (CNS).
Main Methods:
- Rats received intracerebral injections of Corynebacterium parvum (an inflammatory agent) or saline.
- Mononuclear cells were labeled and injected intravenously.
- Cells from brain hemispheres were analyzed using flow cytometry and immunohistochemistry.
- Monocytes were identified using OX-42 antibody labeling.
Main Results:
- Monocyte infiltration was observed in both ipsilateral and contralateral hemispheres after C. parvum injection.
- No significant cell extravasation into the brain occurred in saline-injected control rats.
- Macrophages were abundant in the ipsilateral hemisphere.
- Monocytes were confirmed to enter the brain from the bloodstream.
Conclusions:
- The brain permits monocyte homing to both hemispheres following unilateral inflammatory insult.
- Monocyte infiltration into the brain is a delayed process compared to non-neural tissues.