[Therapeutic strategy for peripheral nerve regeneration; molecular permeability control at the blood-nerve barrier]

The blood-nerve barrier (BNB) is one of the functional barriers sheltering the nervous system from systemic blood. Although BNB is effective in controlling the endoneurial environment in normal condition, it may interfere the entrance of beneficial substances including various growth factors into the endoneurial space and inhibit the axonal regeneration in peripheral neuropathy. Since endothelial cells and pericytes of endoneurial microvascular origin are structural basis of BNB, investigation of the characteristics of these two cells using cell culture technique may provide novel strategies to modify BNB functions to promote peripheral nerve regeneration; however, no adequate cell lines possessing in vivo BNB characteristics were present so far. Recently we successfully established cell lines of endothelial cells and pericytes of endoneurial microvessel origin using transgenic rats harboring the temperature-sensitive simian virus 40 large T antigen. We also obtained immortal endothelial and pericyte cell lines originating from human BNB. Analyses of physiological characteristics and protein profiles in these BNB-forming cells are underway in our laboratory.