UCSF

Traumatic brain injury (TBI) activates the simultaneous proliferation of various pro- and anti-inflammatory molecules. Considering the amount of factors participating, this response is naturally complex. However, there is an increasing trend in neurotrauma research to delineate the injury-induced inflammatory responses within the constraints of in vitro defined macrophage polarization phenotypes "M1" and "M2". Here, we evaluate research examining the complexity of the inflammatory response that cannot be so easily characterized using this binary nomenclature. TBI is demonstrated to induce a broad spectrum of simultaneous expression responses involving both pro- and anti-inflammatory reactions. Specifically, the research revealed a very heterogeneous parenchymal landscape associated with TBI. The concurrent expression of both "M1" and "M2" phenotypic markers on the microglia/macrophages involved suggests that the polarization phenotypes cannot be neatly defined in this M1/M2 paradigm. Recent studies displaying neurotrauma also report similar conflict with the constraints of this binary categorization of "M1/M2", demonstrating that microglia/macrophages cannot effectively cross-over to strictly polarized "M1-only" or "M2-only" phenotype. Therefore, the complex signaling events surrounding this response indicate that a binary M1/M2 characterization is not adequate to define inflammatory profile. This paper is a review article. Referred literature in this paper has been listed in the references part. The datasets supporting the conclusions of this article are available online by searching the PubMed. Some original points in this article come from the laboratory practice in our research centers and the authors' experiences.