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Published on: January 30, 2014
Microglia and astroglia proliferation within the normal appearing white matter in histologically active and inactive
Przemysław Nowacki1, Dorota Koziarska1, Marta Masztalewicz1
1Department of Neurology, Pomeranian Medical University, Szczecin, Poland.
Introduction:
Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease with the involvement of white and grey matter. Histopathological abnormalities can be also identified in normal appearing white matter (NAWM).
Aim Of The Study:
To compare the micro- and astroglia proliferation within NAWM in MS cases with and without inflammatory activity within central nervous system (CNS).
Material And Methods:
In post-mortem brain examinations we investigated 13 MS cases and 5 individuals who suddenly died for cardiological reasons without neurological comorbidities. We analysed micro- and astroglia proliferation within NAWM in histologically active and inactive MS cases in relation to the control group. To avoid the possible influence of the modern disease modifying treatment (DMT) on NAWM histopathological appearance, we decided to investigate the individuals who died before the modern DMT was introduced in Poland. The morphometric analysis of micro- and astrogliosis was carried out at magnification 10 × 10 (microscopic lens × oculars = magnification 100×). The fields were expressed in mm2; each field = 0.364 mm2. In total, 775 fields of NAWM and 420 fields of white matter in the control group were morphometrically assessed.
Results:
Significantly higher microglia proliferation appeared both in MS active and inactive cases compared to controls, while there were no differences between active and inactive cases. There was a significantly higher proliferation within NAWM of active MS cases compared to the inactive ones and controls as well as between inactive cases and controls. There were no correlations between microglia and astrocytes proliferation either in active or inactive MS groups.
Conclusions:
Our results suggest that within MS NAWM, which appears to be involved at the very least, intense diffuse micro- and astroglia reactions occur. Possibly, microglia rather support proinflammatory mechanisms, whereas astrocytes seem to be more neuroprotective. Diffuse microglia proliferation indicates that CNS immune system is chronically activated within the whole CNS.
Insights
Multiple sclerosis (MS) involves chronic central nervous system (CNS) immune activation, with significant microglia and astrocyte proliferation in normal-appearing white matter (NAWM) in both active and inactive MS cases compared to controls.
Area of Science:
- Neuroimmunology
- Neurodegeneration
- Histopathology
Background:
- Multiple sclerosis (MS) is an autoimmune neurodegenerative disease affecting both white and grey matter.
- Histopathological abnormalities are present even in normal-appearing white matter (NAWM) in MS.
- Understanding glial cell behavior in NAWM is crucial for MS pathogenesis.
Purpose of the Study:
- To compare micro- and astroglia proliferation in NAWM in MS with and without central nervous system (CNS) inflammatory activity.
- To investigate glial responses in NAWM in pre-modern disease-modifying treatment (DMT) era MS cases.
Main Methods:
- Post-mortem brain examination of 13 MS cases and 5 controls.
- Morphometric analysis of microglia and astrocyte proliferation in NAWM.
- Comparison between histologically active MS, inactive MS, and control groups.
Main Results:
- Significantly higher microglia proliferation in NAWM in both active and inactive MS cases compared to controls.
- No significant difference in microglia proliferation between active and inactive MS cases.
- Significantly higher astrocyte proliferation in NAWM in active MS cases compared to inactive MS and controls.
Conclusions:
- Intense, diffuse micro- and astroglia reactions occur in MS NAWM, indicating chronic CNS immune activation.
- Microglia may promote pro-inflammatory mechanisms, while astrocytes might offer neuroprotection in MS.
- NAWM is significantly involved in MS pathogenesis, even when appearing normal.
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