Table 1.
Glial response and neurodegeneration in multiple sclerosis plaques
| Plaque | Histologic features | Axon | Astrocyte | M/M | OL-linage cells |
|---|---|---|---|---|---|
| Active (acute) | Indistinct edge, hypercellularity, edema, intense perivascular infiltration (Lucchinetti et al., 1999; Trapp et al., 1999; Kornek et al., 2000; Frohman et al., 2006; Patrikios et al., 2006) | Widespread axonal degeneration throughout the lesion (Trapp et al., 1998; Lucchinetti et al., 1999; Kornek et al., 2000; Frohman et al., 2006; Patrikios et al., 2006) | Hypertrophic astrocytes, little/ no astroglial scar (Frohman et al., 2006) | Abundant myelin-laden M/M evenly distributed throughout the lesion, M/M at the edge extend processes to myelin internodes, pro-inflammatory phenotype at early stage and intermediate phenotype at later stage (Trapp et al., 1999; Kornek et al., 2000; Frohman et al., 2006; Patrikios et al., 2006; Bramow et al., 2010; Schultz et al., 2017; Zrzavy et al., 2017) | Demyelination, variably reduced OLs, but some with sufficient OPCs, occasional remyelination (Lucchinetti et al., 1999; Frohman et al., 2006; Boyd et al., 2013) |
| Chronic active | Sharp edge, hypocellular core with glial scar, hypercellular edge with perivascular cuffs of infiltrates (Frohman et al., 2006) | Demyelinated axons in the core, transected axons and small ovoids at the border (Trapp et al.,1998; Kornek et al., 2000; Frohman et al., 2006) | Astroglial scar in the core, hypertrophic astrocytes at the border (Frohman et al., 2006) | Some myelin-laden M/M in the core, a rim of M/M with empty vacuoles at the border in pro-inflammatory phenotype (Trapp et al., 1999; Kornek et al., 2000; Frohman et al., 2006; Bramow et al., 2010; Zrzavy et al., 2017) | Complete demyelination, few OLs nor OPCs, some remyelination at the border (Lucchinetti et al., 1999; Frohman et al., 2006; Boyd et al., 2013) |
| Chronic inactive | Sharp edge, hypocellularity, hyalinized vessels, no ongoing myelin destruction at the border (Lucchinetti et al., 1999; Kornek et al., 2000; Frohman et al., 2006; Popescu et al., 2013) | Reduced number of demyelinated axons embedded in glial scar, substantial axonal degeneration/loss (Kornek et al., 2000; Frohman et al., 2006; Popescu et al., 2013) | Astroglial scar (Frohman et al., 2006; Popescu et al., 2013) | Few M/M (Trapp et al., 1999; Kornek et al., 2000; Frohman et al., 2006; Bramow et al., 2010; Schultz et al., 2017; Zrzavy et al., 2017) | Complete demyelination, absent remyelination, substantial OL loss, but some with sufficient OPCs (Lucchinetti et al., 1999; Frohman et al., 2006; Boyd et al., 2013; Popescu et al., 2013) |
| Remyelinated (shadow) | Sharp edge, myelin pallor due to abnormally thin myelin sheaths (Lucchinetti et al., 1999; Kornek et al., 2000; Patrikios et al., 2006; Bramow et al., 2010; Schultz et al., 2017) | No significant axonal degeneration, abundant axons with thin myelin sheath (Lucchinetti et al., 1999; Kornek et al., 2000; Patrikios et al., 2006) | Some astroglial scar (Lucchinetti et al., 1999) | Few M/M (Lucchinetti et al., 1999; Kornek et al., 2000; Patrikios et al., 2006; Bramow et al., 2010; Schultz et al., 2017) | Over 60% remyelinated area, OL reappearance, uniformly thin myelin sheath, pronounced expression of PLP in OLs (Lucchinetti et al., 1999; Kornek et al., 2000; Bramow et al., 2010) |
M/M: Microglia/macrophage; NAWM: normal appearing white matter; OL: oligodendrocyte; PLP: proteolipid protein.