Contributions
Abstract: 239
Type: Free Communications
Abstract Category: Pathology and pathogenesis of MS - Pathology
Introduction: Subpial cortical pathology in multiple sclerosis (MS), an important contributor to the disease progression, exhibits a 'surface-in' gradient of damage, likely mediated by diffusion of soluble CSF myelinotoxic and inflammatory factors from the subarachnoid space towards the cortex.
Aim: We intend to elucidated whether a similar gradient of damage may also involve the thalamus, a subcortical gray matter structure with two distinct interfaces (the white matter and the ventricular surface), which exhibits an early and prominent contribution to MS pathology.
Methods: By using immunohistochemistry on post-mortem thalamic medial nuclei from 5 healthy controls and 10 SPMS cases, detailed counts of total cells, MHC-class II+ activated microglia and NeuN+ neurons were performed. In addition, specific characterization of different microglia/macrophage phenotypes was achieved.
Results: A gradient of cell count changes was found both in thalamic lesions (TL) and in normal appearing thalamic areas (NAT) from the subependymal surface close to CSF towards the white matter (WM) in the same SPMS cases showing a “surface-in” gradient of cortical damage. The highest alterations were detected up to 4 mm from the CSF/thalamus interface and included increased microglia density (80% increase in TL vs Ctrl; 60% in NAT vs Ctrl), diminishing towards WM (30% in TM; 20% in NAT). In particular, substantial proportion of MHC-II+ microglia detected close to CSF surface was found to express TMEM119, marker of resident microglia activation, while only a minor fraction expressed CD68, CD86 and CD163 markers. In contrast, decreased density of NeuN+ neurons was found from the subependimal surface (40% decrease in TL vs Ctrl; 25% in NAT vs Ctrl) towards the inner regions (20% in TL vs Ctrl; 10% in NAT vs Ctrl). Interestingly, negative correlation (r= -0.51; p< 0.01) was found between neuronal loss and microglia activation according to the distance from CSF, while no correlations have been found when total cells have been correlated.
Conclusions: A graded injury (notable for microglial activation and neuronal loss) characterizes both lesional and normal appearing thalamic tissues in progressive MS patients, a finding consistent with a “subependymal-in” gradient, specular to the “surface-in” pattern of subpial cortical injury. These data provide further evidence of intrathecal, compartmentalized inflammation that may drive cortical and subcortical gray matter MS damage.
Disclosure: Roberta Magliozzi: nothing to disclose
Abstract: 239
Type: Free Communications
Abstract Category: Pathology and pathogenesis of MS - Pathology
Introduction: Subpial cortical pathology in multiple sclerosis (MS), an important contributor to the disease progression, exhibits a 'surface-in' gradient of damage, likely mediated by diffusion of soluble CSF myelinotoxic and inflammatory factors from the subarachnoid space towards the cortex.
Aim: We intend to elucidated whether a similar gradient of damage may also involve the thalamus, a subcortical gray matter structure with two distinct interfaces (the white matter and the ventricular surface), which exhibits an early and prominent contribution to MS pathology.
Methods: By using immunohistochemistry on post-mortem thalamic medial nuclei from 5 healthy controls and 10 SPMS cases, detailed counts of total cells, MHC-class II+ activated microglia and NeuN+ neurons were performed. In addition, specific characterization of different microglia/macrophage phenotypes was achieved.
Results: A gradient of cell count changes was found both in thalamic lesions (TL) and in normal appearing thalamic areas (NAT) from the subependymal surface close to CSF towards the white matter (WM) in the same SPMS cases showing a “surface-in” gradient of cortical damage. The highest alterations were detected up to 4 mm from the CSF/thalamus interface and included increased microglia density (80% increase in TL vs Ctrl; 60% in NAT vs Ctrl), diminishing towards WM (30% in TM; 20% in NAT). In particular, substantial proportion of MHC-II+ microglia detected close to CSF surface was found to express TMEM119, marker of resident microglia activation, while only a minor fraction expressed CD68, CD86 and CD163 markers. In contrast, decreased density of NeuN+ neurons was found from the subependimal surface (40% decrease in TL vs Ctrl; 25% in NAT vs Ctrl) towards the inner regions (20% in TL vs Ctrl; 10% in NAT vs Ctrl). Interestingly, negative correlation (r= -0.51; p< 0.01) was found between neuronal loss and microglia activation according to the distance from CSF, while no correlations have been found when total cells have been correlated.
Conclusions: A graded injury (notable for microglial activation and neuronal loss) characterizes both lesional and normal appearing thalamic tissues in progressive MS patients, a finding consistent with a “subependymal-in” gradient, specular to the “surface-in” pattern of subpial cortical injury. These data provide further evidence of intrathecal, compartmentalized inflammation that may drive cortical and subcortical gray matter MS damage.
Disclosure: Roberta Magliozzi: nothing to disclose