Neurotrauma: 2021 update

Abstract

Despite the interruptions and restrictions to the progress of science that the COVID-19 pandemic has introduced, 2020 was marked by a number of important advances in the field of neurotrauma. Here, I will highlight what I believe are among the most important contributions. This year there were notable advances towards providing clinically useful information on neurotrauma outcome through the use of fluid biomarkers. I also introduce fascinating approaches to studying the role of microglia in nervous system repair and neuroinflammatory mechanisms leading to dysfunction through the use of colony-stimulating factor 1 receptor inhibitors, especially Plexxikon 5622 (PLX5622). Oral administration of this compound is able to deplete microglial elements and then, following withdrawal from the drug, a new population of microglia then repopulates the brain. Use of this approach in traumatic brain injury experimental models has produced important insights into the pathogenetic role of microglia in responding to this process. Important new data on the nature and distribution of tau involvement of neurons and astrocytes in cases of chronic traumatic encephalopathy (CTE) also appeared suggesting differences and similarities to Alzheimer s disease. Additionally, the use of tau-specific PET scan ligands in at-risk populations has suggested that this approach may be able to identify cases with CTE. Lastly, we note the death in the past year of a major contributor to the field of neurotrauma neuropathology, Professor J. Hume Adams.

Keywords: Biomarkers; Chronic traumatic encephalopathy; Microglia; Neuroinflammation; Tau; Traumatic brain injury.

Figure 1

Microglia are depicted in 8 weeks old CX3CR1-GFP mice (microglia – green; DAPI – blue) A) control mouse, normal diet, B) 3 weeks following a diet containing 1200 mg/kg of PLX5622 (note virtual complete absence of microglia) and C) after 3 weeks on the PLX5622 diet then 2 weeks on the control diet (note the return of prominent green staining from the repopulated microglia). From ongoing studies of K. Whiting and Z. Galdzicki of Uniformed Service University - Neurosciences Program.

Figure 2

Breaching is a procedure whereby an explosive charge, typically placed on a door, is used by combatants to enter a building and engage the enemy. Service Members participate in breaching in both training exercises and on the field of battle. Repeated training exercises, such as portrayed here, expose participants to numerous sub-concussive blast wave exposures, in the absence of impact TBI. Courtesy of Sofia Echelmeyer.