The role of neutrophils in vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: Is it time for a SAH clinical trial targeting neutrophils?

Abstract

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological disease, and one of the primary drivers of morbidity after aneurysm rupture is the phenomenon of delayed cerebral ischemia (DCI). Significant knowledge has been gained over the past two decades of the impact of neuroinflammation in DCI; and neutrophils are now believed to play a major role. There is significant human subject data showing the rise of neutrophil related inflammatory markers and neutrophil’s association with poor outcome after aSAH, but as of yet no trials involving human subjects have been done specifically targeting neutrophils. There is however a growing body of evidence in animals models that targeting neutrophils, or their byproducts such as neutrophil extracellular traps improves outcomes. This review summarizes the available evidence of neutrophil’s impact in both human subjects and animal models of aSAH and should serve as an impetuous to explore clinical trials in human subjects.