Inflammatory responses in Multiple Sclerosis normal-appearing white matter and in non-immune mediated neurological conditions with wallerian axonal degeneration: A comparative study

Inflammatory-like changes in the white matter (WM) are commonly observed in conditions of axonal degeneration by different etiologies. This study is a systematic comparison of the principal features of the inflammatory-like changes in the WM in different pathological conditions characterized by axonal damage/degeneration, focusing in particular on Multiple Sclerosis (MS) normal-appearing white matter (NAWM) compared to non immune-mediated disorders. The study was performed on sections of NAWM from 15 MS cases, 11 cases of non immune-mediated disorders with wallerian axonal degeneration (stroke, trauma, amyotrophic lateral sclerosis), 3 cases of viral encephalitis, 6 control cases. Common features of the inflammatory-like changes observed in all of the conditions of WM pathology were diffuse endothelial expression of VCAM-1, microglial activation with expression of M2 markers, increased expression of sphingosine receptors. Inflammation in MS NAWM was characterized, compared to non immune-mediated conditions, by higher VCAM-1 expression, higher density of perivascular lymphocytes, focal perivascular inflammation with microglial expression of M1 markers, ongoing acute axonal damage correlating with VCAM-1 expression but not with microglia activation. Inflammatory changes in MS NAWM share all the main features observed in the WM in non immune-mediated conditions with wallerian axonal degeneration (with differences to a large extent more quantitative than qualitative), but with superimposition of disease-specific perivascular inflammation and ongoing acute axonal damage.