The protective role of nuclear Heme oxygenase-1 in blood-spinal cord barrier after hypoxia in vitro.

Spinal cord injury (SCI), which results in severe lower-limb motor dysfunction, is a neurological disorder that damages the central nervous system. Disruption of the blood-spinal cord barrier (BSCB) results in secondary injury and neuronal apoptosis. Thus, this study aimed to investigate the effect of nuclear heme oxygenase-1 (HO-1) on BSCB after hypoxia in an in vitro model and to identify the potential regulatory mechanism of nuclear HO-1 (nHO-1) in BSCB. In an in vitro hypoxia model, nHO-1 treatment attenuated BSCB permeability. In addition, western blot analysis indicated that the expression levels of tight junction-associated proteins (ZO-1, occludin) and adherens junction-associated proteins (VE-cadherin) increased after treatment with nHO-1. Reverse transcription quantitative PCR assay showed that the mRNA levels of these proteins were remarkable in cells overexpressing nHO-1. The immunofluorescence staining of ZO-1 showed a similar trend. Our data indicated that nHO-1 decreased the number of TUNEL-positive cells. Therefore, nHO-1 could decrease the permeability of the BSCB by promoting the protein expression levels of ZO-1, occludin, and VE-cadherin and by reducing the apoptosis of spinal cord microvascular endothelial cells. Our study provides new insights into the molecular mechanism by which nHO-1 regulates BSCB after SCI, demonstrating that nHO-1 may be a viable target for the treatment of SCI.