Therapeutic Time Window for rt-PA Thrombolysis in a Rat Photothrombotic Ischemic Stroke Model

Abstract

The narrow 3h therapeutic time window for recombinant tissue-type plasminogen activator (rt-PA) thrombolysis is a challenging limitation in acute ischemic stroke treatment. Intense research focus is being laid on developing novel therapeutic interventions for extending the thrombolysis time window using animal stroke models. However, these animal models are anatomically and physiologically different. Here, we assess the effective time window of rt-PA thrombolysis in the photothrombotic ischemic (PTI) stroke model using the electrocorticography (ECoG) system and histology study. Our results indicate that rt-PA provides effective thrombolysis when administered in the initial 1 to 3 hours post-ischemia, beyond which it does not facilitate recovery. This complements the FDA-approved rt-PA time window in humans. However, it is interesting to note that the trend of neural activity did not strictly correspond to infarct volume changes, indicating the importance of multimodal imaging for holistic assessment of therapeutic efficacy. Therefore, in the future, this ECoG setup will be integrated with the functional photoacoustic microscopy (fPAM) system to jointly evaluate neural activity and cerebral hemodynamics to probe neurovascular function changes effective with thrombolysis.