Polymorphonuclear neutrophil infiltration into ischemic infarctions: myth or truth?

Excerpt

Knowledge builds on steps considered scientific truths, which shall endure the test of time and variations in circumstances. For decades, neuropathologists have used the sequence of cellular changes including immune cell reaction in infarcted brain tissue for timing the development of the infarction [1, 13]. A generally accepted concept has been that polymorphonuclear neutrophils (PMN) can cause plugging of microvessels within the vascular territory of an occluded artery even when reperfused [2], and they extravasate and invade the brain parenchyma at early stages of infarction (within 15–24 h; e.g., [1, 10, 11, 13, 15, 17]. The infiltration of PMNs into ischemic infarcts has led to the hypothesis that besides adhering to the endothelium and plugging microvessels before extravasation (no-reflow phenomenon), PMNs release a palette of neurotoxic substances, which contribute to neuronal cell death as a component of ischemia–reperfusion injury. Having been confirmed in many experimental brain ischemia studies, this hypothesis has stimulated trials of therapeutic interventions based on combatting this PMN response by various means (e.g., [5, 14]). Such therapeutic trials targeting PMNs have given inconsistent results in both experimental studies and clinical trials. …