The Polarization States of Microglia in TBI: A New Paradigm for Pharmacological Intervention

Abstract

Traumatic brain injury (TBI) is a serious medical and social problem worldwide. Because of the complex pathophysiological mechanisms of TBI, effective pharmacotherapy is still lacking. The microglial cells are resident tissue macrophages located in the brain and have two major polarization states, M1 phenotype and M2 phenotype, when activated. The M1 phenotype is related to the release of proinflammatory cytokines and secondary brain injury, while the M2 phenotype has been proved to be responsible for the release of anti-inflammation cytokines and for central nervous system (CNS) repair. In animal models, pharmacological strategies inhibiting the M1 phenotype and promoting the M2 phenotype of microglial cells could alleviate cerebral damage and improve neurological function recovery after TBI. In this review, we aimed to summarize the current knowledge about the pathological significance of microglial M1/M2 polarization in the pathophysiology of TBI. In addition, we reviewed several drugs that have provided neuroprotective effects against brain injury following TBI by altering the polarization states of the microglia. We emphasized that future investigation of the regulation mechanisms of microglial M1/M2 polarization in TBI is anticipated, which could contribute to the development of new targets of pharmacological intervention in TBI.

Acute exposure to diesel exhaust impairs adult neurogenesis in mice: prominence in males and protective effect of pioglitazone

“…Reactive microglia have greater cell body area and thicker, shorter processes (Jonas et al 2012; Morrison and Filosa 2013; Torres-Platas et al 2014). It should be noted that microglia may either promote or inhibit adult neurogenesis (Sato 2015), depending on the activation state (Aarum et al 2003; Xu et al 2017). Notably, the M2 activation state, which is induced by anti-inflammatory cytokines such as IL-4, favors proliferation, and can direct neural progenitor cells (NPC) towards neurogenesis (Cherry et al 2014; Choi et al 2017; Zhao et al 2017).…”

SIV Latency in Macrophages in the CNS

“…Polarization has been mainly explored in bone marrow-derived MDMs in vitro; while in vivo macrophages are incredibly heterogeneous, and likely exist along a continuum of the M1-M2 spectrum.. During inflammatory and infectious processes, there is a major influx of monocytes into tissues (75, 76), making it difficult to demonstrate that shifts in polarization are occurring in resident cells and not in recently arrived monocytes. Recent studies on brain macrophages show that microglia respond to cytokine stimulation similar to MDMs (77–79). While the concepts described by in vitro studies have been useful in tissue macrophages (72–74), direct translation of these studies has not been comprehensively explored in vivo (80).…”

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

“…In the injured brain, microglia can produce neuroprotective factors, clear cellular debris, and orchestrate neurorestorative processes that are beneficial for neurological recovery after TBI [100,101]. Microglia can polarize into distinct phenotypes, depending on the microenvironment in which they are activated.…”