Epigallocatechin Gallate Extends the Therapeutic Window of Recombinant Tissue Plasminogen Activator Treatment in Ischemic Rats.
Sleutelwoorden
Abstract
BACKGROUND
Ischemic stroke is the leading cause of death and disability worldwide. To date, recombinant tissue plasminogen activator (rt-PA) remains the only safe and effective pharmaceutical treatment for brain ischemia, but delayed rt-PA administration leads to hyperperfusion, which severely limits its clinical efficacy.
METHODS
In this study, we investigated the effect of epigallocatechin gallate (EGCG) in extending the therapeutic window of rt-PA using a rat middle cerebral artery occlusion (MCAO) model.
RESULTS
Simultaneous treatment of EGCG and rt-PA significantly recovered the neurobehavioral deficit, when administered even 4 hours after MCAO. Pathological examinations on the ischemic brain samples revealed that EGCG significantly alleviated the common side effects of delayed rt-PA treatment, including brain infarction, cerebral edema, and blood-brain barrier disruption. We further found that EGCG exerted its protective functions against delayed rt-PA through upregulation of plasminogen activator inhibitor-1, as well as downregulation of matrix metalloproteinases.
CONCLUSIONS
Our study has demonstrated for the first time in vivo results supporting the potential of EGCG to be coadministered with rt-PA, to extend its therapeutic window in treating acute brain ischemia.
