3.1.1 Ultrastructural modifications
In postmortem ALS human spinal cord, electron microscopy and
immunohistochemistry revealed swelling and cytoplasmic vacuolisation of
microvascular endothelial cells, degeneration of pericytes and
detachment of astrocyte end-feet processes from endothelial cells
(Garbuzova-Davis et al., 2012; Miyazaki et al., 2011; Sasaki, 2015;
Yamadera et al., 2015). Studies also reported increased (Garbuzova-Davis
et al., 2012; Waters et al., 2021) or decreased (Miyazaki et al., 2011;
Ono et al., 1998) collagen content in the basement membrane of the
spinal cord microvasculature in ALS patients. Reduced collagen content
in the basement membrane can be to due cellular damage, whereas a
thickened basement membrane could be a result of repetitive
regeneration. This discrepancy in the above reports could be attributed
to the different CNS regions assessed, the heterogeneity in ALS
pathology, and varied quantification methods employed to assess collagen
content. Further studies are required to confirm this in a more
systematic manner, and assess the impact of basement thickening or
thinning on CNS exposure of passively-diffusing compounds, given that
brain microvascular basement membrane thickening has been associated
with reduced BBB transport of passively-diffusing drugs in a mouse model
of AD (Mehta, Short & Nicolazzo, 2013).