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

Gamma glutamyl transpeptidase (gammaGT) 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 gammaGT 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, gammaGT 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 gammaGT activity in rat brain endothelial (RBE4) cells. Tumor necrosis factor alpha and lipopolyssachride significantly increased gammaGT 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 gammaGT activity reflect evolving changes of endothelial function.