Call Off the Dog(ma): M1/M2 Polarization Is Concurrent following Traumatic Brain Injury

Following the primary mechanical impact, traumatic brain injury (TBI) induces the simultaneous production of a variety of pro-and anti-inflammatory molecular mediators. Given the variety of cell types and their requisite expression of cognate receptors this creates a highly complex inflammatory milieu. Increasingly in neurotrauma research there has been an effort to define injury-induced inflammatory responses within the context of in vitro defined macrophage polarization phenotypes, known as M1 and M2. Herein, we expand upon our previous work in a rodent model of TBI to show that the categorization of inflammatory response cannot be so easily delineated using this nomenclature. Specifically, we show that TBI elicited a wide spectrum of concurrent expression responses within both pro-and anti-inflammatory arms. Moreover, we show that the cells principally responsible for the production of these inflammatory mediators, microglia/macrophages, simultaneously express both M1 and M2 phenotypic markers. Overall, these data align with recent reports suggesting thatmicroglia/macrophages cannot adequately switch to a polarized M1-only or M2-only phenotype, but display a mixed phenotype due to the complex signaling events surrounding them.