Neuroinflammation as a key driver of secondary neurodegeneration following stroke?

Abstract

Ischaemic stroke involves the rapid onset of focal neurological dysfunction, most commonly due to an arterial blockage in a specific region of the brain. Stroke is a leading cause of death and common cause of disability, with over 17 million people worldwide suffering from a stroke each year. It is now well‐documented that neuroinflammation and immune mediators play a key role in acute and long‐term neuronal tissue damage and healing, not only in the infarct core but also in distal regions. Importantly, in these distal regions, termed sites of secondary neurodegeneration (SND), spikes in neuroinflammation may be seen sometime after the initial stroke onset, but prior to the presence of the neuronal tissue damage within these regions. However, it is key to acknowledge that, despite the mounting information describing neuroinflammation following ischaemic stroke, the exact mechanisms whereby inflammatory cells and their mediators drive strokeinduced neuroinflammation are still not fully understood. As a result, current anti‐inflammatory treatments have failed to show efficacy in clinical trials. In this review we discuss the complexities of post‐stroke neuroinflammation, specifically how it affects neuronal tissue and post‐stroke outcome acutely, chronically, and in sites of SND. We then discuss current and previously assessed anti‐inflammatory therapies, with a particular focus on how failed anti‐inflammatories may be repurposed to target SND‐associated neuroinflammation.