Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Jun 2012
ReviewRelevance of endothelial junctions in leukocyte extravasation and vascular permeability.
Inflammation and immune surveillance rely on the ability of leukocytes to leave the blood stream and enter tissue. Cytokines and chemokines regulate expression and the activation state of adhesion molecules that enable leukocytes to adhere and arrest at sites of leukocyte exit. ⋯ This work has revealed the dominant importance of the junctional pathway between endothelial cells in vivo. In addition, recent progress has improved our understanding of the molecular mechanisms that regulate junctional stability, the opening of endothelial junctions during leukocyte extravasation, and the induction of vascular permeability.
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Ann. N. Y. Acad. Sci. · Jun 2012
Modulation of tight junction proteins in the perineurium for regional pain control.
Peripheral neurons are surrounded by the perineurium that forms the blood-nerve barrier and protects the nerve. Although the barrier serves as protection, it also hampers drug delivery of analgesic drugs to the peripheral nerve. We previously showed that opening of the barrier using hypertonic solutions facilitates drug delivery, for example, of hydrophilic opioids, which selectively target nociceptors. ⋯ After several days, tight junction proteins reappear and the barrier reseals. Similarly, perineurial injection of hypertonic saline transiently opens the barrier, claudin-1 disappears, and hydrophilic analgesic drugs are effective. In the future, these findings could be used to reseal the barrier breakdown and could be applied to other barriers like the blood-brain or the intestinal mucosal barrier.