Glial cells react to closed head injury in a distinct and spatiotemporally orchestrated manner

Abstract

Traumatic brain injury (TBI) is a leading cause of mortality and disability worldwide. Acute neuroinflammation is a prominent reaction after TBI and is mostly initiated by brain-resident glial cells such as microglia, NG2-glia and astrocytes. The magnitude of this reaction paves the way for long-lasting consequences such as chronic neurological pathologies, for which therapeutic options remain limited. The neuroinflammatory response to TBI is mostly studied with craniotomy-based animal models that are very robust but also rather artificial. Here, we aimed to analyze the reaction of glial cells in a highly translational but variable closed head injury (CHI) model and were able to correlate the severity of the trauma to the degree of glial response. Furthermore, we could show that the different glial cell types react in a temporally and spatially orchestrated manner in terms of morphological changes, proliferation, and cell numbers in the first 15 days after the lesion. Interestingly, NG2-glia, the only proliferating cells in the healthy brain parenchyma, divided at a rate that was correlated with the size of the injury. Our findings describe the previously uncharacterized posttraumatic response of the major brain glial cell types in CHI in order to gain a detailed understanding of the course of neuroinflammatory events; such knowledge may open novel avenues for future therapeutic approaches in TBI.