Gamma glutamyl transpeptidase is a dynamic indicator of endothelial response to stroke

Gamma glutamyl transpeptidase (γGT) is enriched at the apical surface of the cerebral capillaries that constitute the blood–brain barrier (BBB). This study tested the effects of hypoxia and inflammation on γGT activity in mice after stroke induced by transient cerebral artery occlusion (tMCAO) and in cultured cerebral microvessel endothelial cells. In microvessel-enriched preparations from mice after tMCAO, γGT activity was higher than in the sham controls in both ipsilateral and contralateral hemispheres from 12 h to 5 days after stroke, but lower at later time points (10–15 days). To identify the roles of different cytotoxic and stimulatory signals in this event, we further studied the dynamic changes of γGT activity in rat brain endothelial (RBE4) cells. Tumor necrosis factor α and lipopolyssachride significantly increased γGT activity in a time-dependent manner, an effect not seen after re-oxygenation. Such endothelial activation correlated with reduced total cellular ATP production. Thus, hypoxia and inflammatory stimulation appeared to have opposite effects on endothelial function. With the co-existence of inflammation and hypoxia in the brain after ischemic stroke, dynamic changes of γGT activity reflect evolving changes of endothelial function.