Inhibition of Proteasomal Glucocorticoid Receptor Degradation Restores Dexamethasone-Mediated Stabilization of the Blood–Brain Barrier After Traumatic Brain Injury*

Abstract

The results indicate that the stabilizing effect of glucocorticoids on the blood-brain barrier is hampered after cerebral lesions by proteasomal glucocorticoid receptor degradation in brain endothelial cells and restored by inhibition of proteasomal degradation pathways. The results provide underlying mechanisms for the clinically observed inefficacy of glucocorticoids. The novel combined treatment strategy might help to attenuate trauma-induced brain edema formation and neuronal damage as secondary effects of brain trauma.