ABSTRACT
To elucidate blood-nerve barrier function and tight-junction protein expression in the dorsal root ganglion (DRG), we analyzed the vascular permeability in the rat DRG by i.v. administration of fluorescent Evans-blue albumin (EBA) and compared it with the localization of claudin-1, claudin-5, and occludin by immunoconfocal microscopy. In the cell body-rich area within the DRG, extravascular leakage of EBA was noted and claudin-5 but neither claudin-1 nor occludin was detected. Conversely, in the nerve fiber-rich area within the DRG, no extravascular leakage of EBA was observed and both claudin-5 and occludin but no claudin-1 were detected in the blood vessel. These results demonstrate regional differences in the blood-nerve barrier function and tight-junction protein expression within the DRG.
Subject(s)
Ganglia, Spinal/metabolism , Ganglia, Spinal/physiology , Nerve Tissue Proteins/biosynthesis , Tight Junctions/metabolism , Tight Junctions/physiology , Animals , Capillary Permeability/physiology , Claudin-1 , Claudin-5 , Evans Blue , Fluorescent Dyes , Immunohistochemistry , Male , Membrane Proteins/metabolism , Microscopy, Confocal , Nerve Tissue Proteins/genetics , Occludin , Rats , Rats, Wistar , von Willebrand Factor/biosynthesis , von Willebrand Factor/geneticsABSTRACT
The blood-nerve barrier in peripheral nerves is important for maintaining the environment for axons. Breakdown of the barrier by nerve injury causes various pathologies. We hypothesized that the breakdown and recovery of the blood-nerve barrier after injury are associated with the changes in the expression of intercellular junctional proteins. To test this hypothesis, we induced crush injuries in the rat sciatic nerve by ligation and analyzed spatiotemporal changes of claudin-1, claudin-5, occludin, VE-cadherin, and connexin43 by immunoconfocal microscopy and morphometry and compared them with changes in the permeability of the blood-nerve barrier by intravenous and local administration of Evans blue-albumin (EBA). On day 1 after removal of the ligature EBA leaked into the connective tissue in the endoneurium and then the leakage gradually decreased and disappeared on day 7. On day 1 claudin-1, claudin-5, occludin, VE-cadherin, and connexin43 had totally disappeared from the perineurium and endoneurium. Thereafter, claudin-1, claudin-5, occludin, and VE-cadherin recovered from day 2, whereas connexin43 was redetected on day 5. These results indicate that the breakdown and following recovery of the blood-nerve barrier are closely associated with changes in the expression of claudins, occludin, VE-cadherin, and connexin43 and that the recovery time course is similar but nonidentical.
