Microglia and astroglia proliferation within the normal appearing white matter in histologically active and inactive multiple sclerosis

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.