Caveolin expression changes in the neurovascular unit after juvenile traumatic brain injury: Signs of blood–brain barrier healing?

Abstract

Traumatic brain injury (TBI) is one of the major causes of death and disability in pediatrics, and results in a complex cascade of events including the disruption of the blood-brain barrier (BBB). A controlled-cortical impact on post-natal 17 day-old rats induced BBB disruption by IgG extravasation from 1 to 3 days after injury and returned to normal at day 7. In parallel, we characterized the expression of three caveolin isoforms, cav-1, cav-2 and cav-3. While cav-1 and cav-2 are expressed on endothelial cells, both cav-1 and cav-3 were found to be present on reactive astrocytes, in vivo and in vitro. Following TBI, cav-1 expression was increased in blood vessels at 1 and 7 days in the perilesional cortex. An increase of vascular cav-2 expression was observed 7 days after TBI. In contrast, astrocytic cav-3 expression decreased 3 and 7 days after TBI. Activation of eNOS (via its phosphorylation) was detected 1 day after TBI and phospho-eNOS was detected both in association with blood vessels and with astrocytes. The molecular changes involving caveolins occurring in endothelial cells following juvenile-TBI might participate, independently of eNOS activation, to a mechanism of BBB repair while, they might subserve other undefined roles in astrocytes.

Loss of mural cell-derived laminin aggravates hemorrhagic brain injury

“…2c, d). Consistent with previous reports that caveolin-1 is predominantly expressed in endothelial cells in the brain [56][57][58][59], caveolin-1 displayed a blood vessel-like pattern in the brain (Fig. 4d).…”

Chronic cerebrovascular dysfunction after traumatic brain injury

“…Its expression is increased in the endothelium during the first week after a cold injury model of TBI (Nag et al, 2007). In support of the phenotypic transformation of the endothelium after juvenile TBI, we observed an increase in cav-1 immunostaining in brain cortical vessels at 2 months postinjury Badaut et al, 2015). This observation also suggests that cav-1 could play a role in the altered claudin-5 and P-gp expression that occur after TBI.…”

Into rather unexplored terrain—transcellular transport across the blood–brain barrier

“…Cavins represent another major caveolar protein family that is implicated in caveolae biogenesis and function (Chidlow and Sessa, ; Hansen and Nichols, ). Caveolae have been endowed with a variety of cellular functions: they are involved in lipid and fatty acid transport, act as a signaling hub linked to G‐protein coupled receptors and eNOS activation and are implicated in mechanosensing (Badaut et al, ; Feng et al, ; Pelligrino and Galea, ; Shvets et al, ). The proposed role of caveolae in transcellular trafficking has been lingering for more than two decades but was underscored by the seminal work of Oh and Schnitzer (Oh et al, ) who indicated the rapid transcellular trafficking of caveolae‐derived vesicles in the lung endothelium in vivo .…”

“…The translocation of iron across the BBB, mediated by transferrin and its receptor, is a typical example of clathrin-dependent endocytosis (Herve et al, 2008;Smith and Gumbleton, 2006). Cav1, Cav2, cavin-1, and cavin-2 have been identified in murine, bovine, and human BBB endothelial cells (Cav3 appears limited to astrocytes) (Badaut et al, 2015;Cornford and Hyman, 2005;Ikezu et al, 1998;Tome et al, 2015;Virgintino et al, 2002). Caveolae have been recognized in both luminal and abluminal membranes, indicating that they mediate transcytosis in both directions (Stamatovic et al, 2011).…”