Reducing myeloperoxidase activity decreases inflammation and increases cellular protection in ischemic stroke.

Myeloperoxidase (MPO) is a pro-inflammatory enzyme abundantly secreted by activated myeloid cells after stroke. We show that when MPO activity is either blocked by the specific inhibitor 4-aminobenzoic acid hydrazide (ABAH) in wildtype (WT) mice or congenitally absent (MPO−/−), there was decreased cell loss, including degenerating neurons and oligodendrocytes, in the ischemic brains compared to vehicle-treated WT mice after stroke. MPO inhibition also reduced the number of activated myeloid cells after ischemia. MPO inhibition increased cytoprotective heat shock protein 70 (Hsp70) by 70% and p-Akt by 60%, while decreased the apoptotic marker p53 level by 62%, compared to vehicle-treated mice after ischemia. Similarly, MPO inhibition increased the number of Hsp70+/NeuN+ cells after stroke by 60%. Notably, MPO inhibition significantly improved neurological outcome compared with the vehicle-treated group after stroke. We further found longer treatment periods resulted in larger reduction of infarct size and ...