The Future of Stroke Neuroprotection

Author(s): David Jonson

There are hundreds of putative Neuroprotectants that have been evaluated in preclinical models, but none have entered the clinical realm, despite the fact that researchers acknowledge the limitations of rodent or non human primate stroke models. In the beginning, research primarily focused on the neuron; however, in more recent years, research has expanded to include astrocytes, pericytes, endothelial cells, and other neural cells that make up the neurovascular unit. There are some new developments that give neuroprotection new hope, new compounds with multiple mechanisms of action or the establishment of new guidelines for stringent preclinical testing In the past five years, only uric acid and nerinetide have been tested for clinical efficacy at the bedside in RCTs, where all patients had to receive reperfusion therapies, such as intravenous thrombolysis or mechanical thrombectomy. Reperfusion therapy was also tested with otaplimastat, 3K3AActivated Protein C (APC), intra arterial verapamil, and intra arterial hypothermia, but only in RCTs with only feasibility or safety outcomes. In this review, some of these compounds are discussed for their promising outcomes. The testing of putative neuroprotectants in enriched clinical studies of patients receiving reperfusion therapies, a better preselection and evaluation of drugs at the preclinical stage, and a deeper understanding of the mechanisms that are involved in the ischaemic death process at the neurovascular unit may prove to be more effective than in the past in reversing a dire situation that has already lasted for an excessive amount of time.