Dynamic roles of neutrophils in post-stroke neuroinflammation

Clinical trials involving the blockage of peripheral inflammatory leukocyte recruitment into the brain have puzzlingly led to either no significant improvement in stroke outcome, or even worsened outcomes and increased mortality, prompting a re-evaluation of our understanding into the neuroinflammatory processes after stroke. Whilst traditionally understood as simple effectors of the innate immune system, emerging research in vascular disease biology has redefined the neutrophil as a specialized and highly specific cell type with dynamic functional capacity. Indeed, emerging experimental evidence indicates that neutrophils display diverse roles in the acute stages of ischemic stroke with the ability to elicit both pro-inflammatory and anti-inflammatory effects. Currently, there is some uncertainty as to whether neutrophil diversity is beneficial or harmful in stroke as their interactions with the resident cells of the brain, such as microglia and neurons, would potentially elicit heterogeneous outcomes. Current treatments for patients with stroke aim to remove the vascular blockage and to restore blood flow, but there are currently no drug treatments for managing the loss of functional brain tissue nor restoration of microglial and neuronal damage. If these hypothesized wound-healing functions of neutrophils can be validated in a stroke setting, promoting the recruitment of this type of neutrophils into the injured brain tissue may form a promising therapeutic target for the majority of stroke patients currently without treatment. In this review, we will provide an update on recent research that has explored neutrophil heterogeneity in the neuroinflammatory cascade after ischemic stroke.

Automated summary

Research on neutrophils in the neuroinflammatory cascade after ischemic stroke indicates their diverse roles in the acute stages, potentially eliciting both pro-inflammatory and anti-inflammatory effects. The uncertainty regarding the benefits or harms of neutrophil diversity in stroke remains, but if their hypothesized wound-healing functions can be validated, it may provide a promising therapeutic target for the majority of stroke patients currently without treatment.