Background
Immune-mediated reperfusion injury is a critical component of post-ischemic central nervous system (CNS) damage. In this context, the activation and recruitment of polymorphonuclear neutrophils (PMNs) to the CNS induces neurotoxicity in part through the release of degradative enzymes, cytokines, and reactive oxygen species. However, the extent to which close-range interactions between PMNs and neurons contribute to injury in this context has not been directly investigated. New method: We devised a co-culture model to investigate mechanisms of PMN-dependent neurotoxicity. Specifically, we established the effect of PMN dose, co-incident neuronal ischemia, lipopolysaccharide (LPS)-induced PMN priming, and the requirement for cell-cell contact on cumulative neuron damage.
Conclusions
Ischemic and immune priming enhance neurotoxicity in PMN-neuronal co-cultures. Moreover, cell-cell contact and neurite destruction are prominent features in the observed mechanism of post-ischemic neuronal death.