Localization of laminin α2 chain in normal human central nervous system: an immunofluorescence and ultrastructural study

Abstract

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.

Congenital muscular dystrophy. Part II: a review of pathogenesis and therapeutic perspectives

“…opposite to the peripheral nerve, in which laminin alpha 2 is associated only with myelinated and not with unmyelinated nerve fibers and is involved in the myelin stability 86 , a role for laminin alpha-2 in central myelination has not been confirmed. Villanova et al 87 found that laminin alpha-2 chain is localized to the basal lamina of all cerebral blood vessels and supposed that it may be important for the selective filtration capability of the bloodbrain barrier. In patients with MDC1A the lack of laminin alpha-2 may lead to an abnormality of the blood-brain barrier causing impaired selective filtration.…”

Inflammation modulates expression of laminin in the central nervous system following ischemic injury

“…Several of the laminin subunits have been shown to be expressed in the rodent brain, including α1 to 5, β1, and γ1 [35,36], and the β3 and γ1 chains have been reported in sprouting neurons and rat astrocytes [37,38]. Laminin α2 is localized in the basal lamina of cerebral blood vessels, and may be important for the selective filtration capability of BBB [39]. The expression of laminin is upregulated in endothelial cells and astrocytes within 24 h following ischemia and stab wounds [40,41].…”

Laminin receptor ?6?4 integrin is highly expressed in ENU-induced glioma in rat

“…binds laminin 2 and 5 with higher affinity than laminin 1, and the expression of laminin 2, 4, and 5 in the proliferative nodules is not characterized; although these laminins have been detected in the developing and adult CNS (Hagg et al, 1997;Villanova et al, 1997;and reviewed in Previtali et al, 1996). Thus, both the ECM and cytoskeletal context could permit ectopic expression of ␣6␤4 to alter the behavior of glioma cells.…”