Protective recombinant glutamate oxaloacetate transaminase increases the benefits of alteplase recanalization therapy in experimental ischaemic stroke

Abstract

The recombinant enzyme glutamate oxaloacetate transaminase (rGOT) has emerged as a promising neuroprotective candidate for acute ischaemic stroke. This study examined whether rGOT can attenuate the neurotoxic side effects of recombinant tissue plasminogen activator (rtPA) and enhance the therapeutic benefit of thrombolytic reperfusion. First, primary cortical neurons were exposed to rtPA with or without rGOT under normoxia or oxygen–glucose deprivation. rGOT did not reduce rtPA-induced cytotoxicity, indicating that the pathways underlying rtPA neurotoxicity are mechanistically distinct from those modulated by rGOT. Second, a thromboembolic mouse model was used to assess the interaction between rGOT and rtPA across clinically relevant treatment scenarios. rGOT alone or when administered prior to rtPA had no effect on infarct size or haemorrhagic transformation. However, co-administration of rGOT with rtPA significantly reduced infarct volume at 24 h (p < 0.05), without increasing bleeding risk. These findings demonstrate that rGOT is compatible with thrombolytic therapy and can enhance rtPA efficacy when delivered during reperfusion, supporting its potential use as an adjuvant treatment in acute ischaemic stroke.