Glial response during adaptive and maladaptive reactive synaptogenesis following traumatic brain injury

Abstract

Neuroglia play an important role in synaptogenesis after traumatic brain injury (TBI). The magnitude of glial response appears to be injury specific, potentially facilitating or attenuating synaptic recovery. Our prior studies also show that matrix metalloproteinases (MMPs) are differentially upregulated within reactive glia as a function of injury. Here, we contrasted glial response in models of adaptive (unilateral entorhinal cortex lesion; UEC) or maladaptive (combined fluid percussion injury and bilateral entorhinal cortex lesion; TBI+BEC) synaptic plasticity. Rats received UEC or TBI+BEC and were sacrificed 7d postinjury. Excised brains were processed for immunohistochemistry (IHC) with antibodies specific to astrocytes (GFAP), microglia (Iba‐1) and membrane‐bound MMPs, ADAM‐10 and MT5‐MMP. Confocal images revealed an increase in GFAP and Iba‐1 over deafferented neuropil in both models compared to uninjured controls. Microglial response was similar in the two models, however, TBI+BEC showed a greater GFAP increase across both dentate molecular and granule cell layers. Only GFAP+ cells were co‐labeled ADAM‐10 and MT5‐MMP. Results suggest that extent and distribution of TBI glial response is injury specific. Moreover, astrocytic ADAM‐10 and MT5‐MMP expression during reactive plasticity is a potential therapeutic target to facilitate synaptogenesis after TBI. Supported by: NIH grants NS44372, NS57758.

The role of ADAM10 in astrocytes: Implications for Alzheimer’s disease

“…In mouse models of traumatic brain injury, which are known to induce a potent inflammatory response, ADAM10 expression has been shown to colocalise with GFAP positive cells ( Del Turco et al, 2014 ). The increased expression of ADAM10 as part of reactive plasticity to brain injury may facilitate synaptogenesis ( Warren et al, 2011 ). The activity of ADAM10 is also increased, shown by elevated N-cadherin cleavage which was linked to reactive gliosis ( Warren et al, 2012 ).…”