Decreased junctional adhesion molecule-A expression during blood-brain barrier breakdown.
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.
Yeung
Dennis
D
Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada.
Manias
Janet L
JL
Stewart
Duncan J
DJ
Nag
Sukriti
S
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051242:Caveolin 1 / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002540:Cerebral Cortex / Q000293:injuries / Q000473:pathology; D003080:Cold Temperature / Q000009:adverse effects; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology* / Q000528:radiation effects; D062726:Junctional Adhesion Molecules; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D051242:Caveolin 1; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D062726:Junctional Adhesion Molecules; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat