UCSF

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 that microglia/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.