Pericyte Protection by Edaravone After Tissue Plasminogen Activator Treatment in Rat Cerebral Ischemia

Pericytes play a pivotal role in contraction, mediating inflammation and regulation of blood flow in the brain. In this study, changes of pericytes in the neurovascular unit (NVU) were examined in relation to the effects of exoge-nous tissue plasminogen activator (tPA) and a free radical scavenger, edaravone. Immunohistochemistry and West-ern blot analyses showed that the overlap between platelet-derived growth factor receptor b-positive peri-cytes and N-acetylglucosamine oligomers (NAGO)-posi-tive endothelial cells increased significantly at 4 days after 90 min of transient middle cerebral artery occlusion (tMCAO). The number of pericytes and the overlap with NAGO decreased with tPA but recovered with edaravone 4 days after tMCAO with proliferation. Thus, tPA treat-ment damaged pericytes, resulting in the detachment from astrocytes and a decrease in glial cell line-derived neurotrophic factor secretion. However, treatment with edaravone greatly improved tPA-induced damage to peri-cytes. The present study demonstrates that exogenous tPA strongly damages pericytes and destroys the integ-rity of the NVU, but edaravone treatment can greatly ameliorate such damage after acute cerebral ischemi