Related Experiment Videos
Expression of the S-100 proteins MRP-8 and -14 in ischemic brain lesions
E Postler1, A Lehr, H Schluesener
1Institute of Brain Research, University of Tübingen, Germany.
Abstract:
So far, microglial activation in cerebral ischemia has only been studied in different animal models. We have investigated the activation of microglial cells in human cerebral ischemia. As a marker for the activation of these "brain macrophages," we have used the macrophage inhibitor factor-related-proteins MRP-8 and MRP-14, which belong to the calcium binding S-100 protein family. The proteins can be detected on microglial cells in bacterial encephalitis and Alzheimer's disease but have so far not been studied in non-inflammatory diseases, in which microglial activation also occurs. Antibodies against MRP-8 and -14 detected ramified microglial cells within the first 3 days after cerebral infarction. Labeled cells were found selectively in the periinfarctional area. To support the notion that these cells belong to the locally activated resident microglial population, we studied their proliferation rate by staining the Ki-67 antigen with the antibody MIB-1. Double-labeling clearly showed that in the early phase of cerebral infarction microglial cells in the periinfarctional area express MRP-8 and -14 and also proliferate. Surprisingly, MRPs are expressed no longer than 3 days post infarction. This indicates that the activation of the resident microglia is an early step of tissue reaction after cerebral infarction. Additionally, we found evidence that microglial cells contribute to the population of phagocytes only during the first 3 days post infarction. The majority of lipid phagocytes found in the later stages are obviously recruited from the blood-borne macrophage pool.
Insights
In human cerebral ischemia, macrophage inhibitor factor-related proteins (MRPs) mark early microglial activation. Resident microglia proliferate and express MRPs within 3 days post-infarction.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Microglial activation in cerebral ischemia is primarily studied in animal models.
- Macrophage inhibitor factor-related proteins (MRPs), specifically MRP-8 and MRP-14, are markers for activated microglial cells.
- Previous studies detected MRPs in inflammatory conditions like encephalitis and Alzheimer's disease, but not in non-inflammatory diseases like cerebral ischemia.
Purpose of the Study:
- To investigate microglial cell activation in human cerebral ischemia.
- To identify specific markers and the temporal dynamics of microglial activation in human stroke.
- To differentiate the roles of resident microglia versus blood-borne macrophages in the ischemic environment.
Main Methods:
- Utilized antibodies against MRP-8 and MRP-14 to detect activated microglial cells in human cerebral infarction samples.
- Employed Ki-67 antigen staining (MIB-1 antibody) to assess the proliferation rate of microglial cells.
- Performed double-labeling techniques to co-localize MRP expression and proliferation within microglial cells in the peri-infarctional area.
Main Results:
- Ramified microglial cells expressing MRP-8 and MRP-14 were identified within the first 3 days post-cerebral infarction, exclusively in the peri-infarctional area.
- Double-labeling confirmed that these MRP-expressing microglial cells in the early phase also proliferate.
- MRP expression was transient, lasting no longer than 3 days post-infarction, suggesting an early role for resident microglia.
Conclusions:
- Microglial activation, marked by MRP expression and proliferation, is an early and transient event in the resident microglia population following human cerebral infarction.
- Resident microglia are the primary phagocytes in the initial 3 days after infarction.
- Later-stage lipid phagocytes are predominantly recruited from the blood-borne macrophage pool, indicating a shift in immune cell involvement.