Post Traumatic Lesion absence of β-Dystroglycan-Immunopositivity in Brain Vessels Coincides with the Glial Reaction and the Immunoreactivity of Vascular Laminin

Abstract

Following brain lesions, the gliovascular basal lamina undergoes destruction and the gliovascular connections 'decouple'. Laminin receptors, as dystroglycan, are essential in these processes. The present study compares the immunoreactivities of beta-dystroglycan, glial fibrillary acidic protein (GFAP), and laminin following stab wounds in adult rats. In intact brain the vessels were immunopositive to beta-dystroglycan, whereas the laminin of their basal lamina proved to be unavailable to immunoreactions. Following stab wound, however, the adjacent vessels lost their immunopositvity to beta-dystroglycan, whereas immunopositivity to laminin became detectable in them. In an advanced stage of glial reaction the territory of GFAP immunopositive reactive astrocytes coincided with the area where vessels lost their immunopositivity to beta-dystroglycan. When glial reaction regressed, the beta-dystroglycan immunopositivity re-appeared, and laminin immunopositivity became undetectable again. Post-lesional disappearance of vascular beta-dystroglycan immunostaining was described earlier, and was attributed to the cleavage of beta-dystroglycan by matrix metalloproteinases as a mechanism of the decoupling of the gliovascular connections. Our results, which were obtained in a different type of lesion support that the loss of vascular beta-dystroglycan immunopositivity is a general phenomenon following cerebral lesions, and an indirect marker of gliovascular decoupling. For the first time coincidences were presented between vascular immunonegativity to beta-dystroglycan, glial reaction and detectability of laminin. Manifestation of laminin immunoreactivity also indicates gliovascular decoupling. Coincidence between glial reaction and lack of vascular beta-dystroglycan suggests mutual enhancement between them. The observations may have clinico-pathologic importance since similar investigations may help to follow the progression and regression of post-lesion processes.

Glial and Perivascular Structures in the Subfornical Organ

“…The pial surface was similar to that found throughout the brain (see, for example, Szabó and Kálmán 2008): its laminin-immunoreactive layer represents the basal lamina toward the pial tissue, whereas the β-dystroglycan immunopositivity is attributed to the attaching subpial glial end-feet.…”

“…The β-dystroglycan subunit is a transmembrane protein that anchors the α-dystroglycan to the membrane of the glial (or other) cells. Its immunoreactivity delineates the brain vessels but not the extracerebral ones (Szabó and Kálmán 2008;Uchino et al, 1996;Zaccaria et al, 2001).The other end of the β-dystroglycan subunit forms a complex with dystrophin, dystrobrevin and other proteins. The complex integrates aquaporin 4 water-channels, ion-channels and signaling systems.…”

Ischemic–hypoxic mechanisms leading to hippocampal dysfunction as a consequence of status epilepticus

“…Damage to astrocytes, cells that contribute to the integrity of the blood-brain barrier, has been associated with a remarkable alteration in the structure of the blood vessel wall [40][41][42]. In the case of pilocarpinetreated rats, we described the presence of microhemorrhages or extravasated erythrocytes around the vessels in CA3 [17] which are neuropathological findings reminiscent of those observed in strokeprone spontaneously hypertensive rats when they developed elevated blood pressure levels [43].…”

“…Interestingly, in both these models, the hemorrhagic lesions were associated with increased immunoreactivity for laminin [17,21], one of the key components of the blood-brain barrier [45]. Alterations in levels of laminin immunoreactivity have also been reported in blood vessel basal lamina following cerebral ischemia [46] or excitotoxic lesions [47,48] and even as a consequence of mechanical lesions [40,41].…”

“…This change in laminin immunoreactivity was interpreted as the consequence of extracellular matrix remodeling subsequent to the loss of the astrocytes that delimited the blood-brain barrier. On the other hand, glial-vascular junctions have been also proposed to limit the accessibility of the basal lamina to antibodies, thus "hiding" the laminin epitopes [40,41]; however, in the presence of vascular damage, the cleavage of β-dystroglycan-laminin complexes by matrix metalloproteinases may lead to disconnection of laminin, making this matrix protein accessible to antibodies. Apart from the dynamics of laminin immunoreactivity increase, the observed changes support the hypothesis that the loss of blood-brain barrier integrity is an early event occurring in the course of SE [50]; this phenomenon could amplify the effects of the primary cause of SE, contributing to the maintenance of epileptic activity even when the primary cause has been removed.…”