Decreased junctional adhesion molecule-A expression during blood–brain barrier breakdown

Abstract

Tight junctions between brain endothelial cells are one of the specialized structural components of the blood-brain barrier (BBB) to proteins. Research in the last decade has demonstrated that the integral membrane proteins of cerebral endothelial tight junctions are claudin, occludin, and junctional adhesion molecule (JAM). Altered expression of these tight junction proteins could cause BBB breakdown following brain injury leading to edema. In this study, expression of JAM-A, was analyzed by immunostaining and immunoblotting in the rat cortical cold injury model, a well-characterized in vivo model of BBB breakdown. Temporal and spatial expression of JAM-A was examined at 12 hours, days 2, 4, and 6 post-lesion in cold-injured and control rats. Control rats showed punctate JAM-A immunoreactivity at intervals along the circumference of the endothelial layer at tight junctions where JAM-A colocalized with occludin. A significant decrease in JAM-A expression was noted at the lesion site by immunoblotting at 12 h only. At this time period, lesion vessels showed loss of endothelial JAM-A immunostaining while day 2 onwards, there was recovery of endothelial JAM-A immunoreactivity. Dual labelling for JAM-A and fibronectin showed that only lesion vessels with BBB breakdown to fibronectin at 12 h also showed lack of endothelial JAM-A immunoreactivity supporting the evidence that JAM-A contributes to tight junction integrity.

Establishment and Characterization of Human Peripheral Nerve Microvascular Endothelial Cell Lines: A New <i>in vitro</i> Blood-Nerve Barrier (BNB) Model

“…FH-BNBs showed spindle fiber morphology and contact inhibition even under the permissive temperature of 33°C, indicating that FH-BNBs, even at the permissive temperature, did not develop a tumor-like phenotype. The endothelial cells forming the BBB express many TJassociated molecules including occludin (Furuse et al, 1993), claudin-1 (Pfeiffer et al, 2011), claudin-5 (Nitta et al, 2003, claudin-12 (Nitta et al, 2003;Ohtsuki et al, 2007), ZO-1, ZO-2 (Biernacki et al, 2004) and JAM-A (Yeung et al, 2008). These molecules compose TJs and limit the paracellular permeability in order to maintain the brain microenvironment.…”

Regulation of Caveolin-1 Expression Determines Early Brain Edema After Experimental Focal Cerebral Ischemia

“…[25][26][27] We proceeded to evaluate whether Cav-1 regulation could induce alterations in tight junction (TJ) protein expression and MMP activity. Figure 5 indicates that transplantation of transfected ECs expressing Cav-1 to Cav-1 −/− mice trends in the direction of reversing the Cav-1 deficiency-induced loss in TJ proteins, including claudin-5, occludin, zona occludens-1, and JAM-A.…”

Cloning and preliminary functional studies of the JAM-A gene in grass carp (Ctenopharyngodon idellus)

“…JAM-A is a broadly expressed immunoglobulin superfamily protein that forms stable homodimers and regulates tight-junction permeability and lymphocyte trafficking [14,15]. The D1 domain (Ig Fig.…”