Potential molecular targets of peroxynitrite in mediating blood-brain barrier damage and haemorrhagic transformation in acute ischaemic stroke with delayed tissue plasminogen activator treatment.

Potential molecular targets of peroxynitrite in mediating blood-brain barrier damage and haemorrhagic transformation in acute ischaemic stroke with delayed tissue plasminogen activator treatment. Free Radic Res. 2018 Nov 23;:1-20 Authors: Chen H, Chen X, Luo Y, Shen J Abstract Tissue plasminogen activator (t-PA) remains to be the only FDA-approved drug for ischaemic stroke, but it has a restrictive therapeutic window with 4.5 hours. Beyond the golden time window, thrombolytic treatment carries the risk of haemorrhagic transformation (HT). The blood-brain barrier (BBB) disruption is a critical step in the t-PA-mediated HT. Although large efforts are made to explore the mechanisms of the BBB disruption and HT, the underlying mechanisms are largely unknown. Thrombolytic treatment for recanalization could produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) and mediate cerebral ischaemia-reperfusion injury. RNS, including nitric oxide (NO) and peroxynitrite (ONOO-), are important players in cerebral ischaemia-reperfusion injury. In particular, ONOO- and its derivatives could mediate neurovascular unit damages and induce the BBB disruption and HT possibly through interacting with different cellular signalling pathways including matrix metalloproteinase (MMPs), high mobility group Box 1 (HMGB1), toll-like receptor2/4, poly(ADP-ribose) polymerase, Src, ROCK, and GSK-3β. Herein, we review current progress about the ro...
Source: Free Radical Research - Category: Research Tags: Free Radic Res Source Type: research