48 Chapter 2 TSPO expression in multiple sclerosis lesions in the cortical grey matter and spinal cord Expression and localisation of TSPO in the grey matter of multiple sclerosis brain was investigated in leukocortical, intracortical, subpial and transcortical lesions (Fig. 3A-I)63. No significant differences were found in the number of cells that express TSPO in grey matter lesions compared to NAGM or to control grey matter (Fig. 3J). HLA-DR+ cells expressing TSPO were not significantly more abundant in the white and grey matter of leukocortical lesions than in the normal appearing white and grey matter or to control tissue (Fig. 3K) and the density of TSPO+HLA-DR+ microglia was low compared to white matter lesions. We observed scattered GFAP+ astrocytes expressing TSPO only in the white matter of leukocortical lesions, similar to those found in purely white matter lesions (Fig. 3C, insert). The density of TSPO+ cells in the NAWM of the spinal cord was no greater than in control spinal cord white matter and neither was the TSPO+ cell density greater in white matter lesions in the spinal cord compared to NAWM or control white matter (Fig. 4A-F). However, the density of TSPO+HLADR+ cells in active white matter lesions was approximately doubled relative to control white matter (P=0.0324; Fig. 4G). Active and chronic active lesions in the spinal cord also showed GFAP+ astrocytes expressing TSPO similar to the brain (Fig. 4C, D, insert; black arrowheads). CON WM NAWM Active CA rim CA centre Inactive 0 100 200 300 400 500 TSPO+HLA-DR+ cells / mm2 * CON WM NAWM Active CA rim CA centre Inactive 0 100 200 300 400 500 TSPO+cells / mm2 Control WM NAWM Active CA rim CA centre Inactive A B C D E F G H TSPO/HLA-DR Figure 4. TSPO expression in white matter lesions in spinal cord. Representative images of TSPO expression in control (A) and multiple sclerosis lesions (B-F); NAWM (B), active (C), CA rim (D) and centre (E), and inactive (F) lesions. Expression of TSPO was found in HLA-DR- cells (black arrowheads; C,D). GFAP+ astrocytes expressing TSPO were also found in the spinal cord (C, insert). Quantitative analysis of the number of TSPO+ cells did not show significant differences between lesion types compared to control or NAWM (G,H). Increased expression of TSPO in HLA-DR+ cells was found in active lesions compared to NAWM (I). *p<0.05. Scale bars (A-F) = 50 μm. Inserts are digitally zoomed in to 800x. CON = control, NAWM = normal appearing white matter, A =active, CA = chronic active, IA = inactive.
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