Localization of laminin alpha 2 chain in normal human central nervous system: an immunofluorescence and ultrastructural study.
Recently, a rare form of congenital muscular dystrophy has been shown to be associated with a deficiency of laminin alpha 2 chain, a tissue-specific component of the basal lamina. Besides muscular dystrophy, children affected with this disorder also show electrophysiological and magnetic resonance imaging evidence of white matter involvement in the central nervous system (CNS). We have studied the precise localization of laminin alpha 2 chain in normal human brain, using specific electron microscopic techniques including thin-section fracture labeling and cryoultramicrotomy, in parallel with immunohistochemical techniques. We found that this laminin chain was localized to the basal lamina of all cerebral blood vessels, whereas blood vessels of the choroid plexus did not show any reaction. No positive reaction was found in meningeal blood vessels either. We hypothesize that in normal brain, laminin alpha 2 may be important for the selective filtration capability of the blood-brain barrier. The lack of laminin alpha 2 in cerebral vessels of children with laminin alpha 2-deficient congenital muscular dystrophy may cause impaired selective filtration, leading to leakage of plasma components and damage to the CNS. Further studies should be performed on patients affected by congenital muscular dystrophy associated with laminin alpha 2 deficiency to test this hypothesis.
Villanova
M
M
Laboratory of Neuropathology, Institute of Neurological Sciences, University of Siena, Italy. villanova@unisi.it
Malandrini
A
A
Sabatelli
P
P
Sewry
C A
CA
Toti
P
P
Torelli
S
S
Six
J
J
Scarfó
G
G
Palma
L
L
Muntoni
F
F
Squarzoni
S
S
Tosi
P
P
Maraldi
N M
NM
Guazzi
G C
GC
D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D006801:Humans; D007231:Infant, Newborn; D007797:Laminin / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D008875:Middle Aged
D007797:Laminin; C102645:laminin alpha 2