Historically, glial cells have been recognized as a structural component of the brain. However, it has become clear that glial cells are intimately involved in the complexities of neural networks and memory formations. Astrocytes, microglia, and oligodendrocytes have dynamic responsibilities which substantially impact neuronal function and activities. Moreover, the importance of glia following brain injury has come to the forefront in discussions to improve axonal regeneration and functional recovery. The numerous activities of glia following injury can either promote recovery or underlie the pathobiology of memory deficits. This review outlines the pathological states of glial cells which evolve from their positive supporting roles to those which disrupt synaptic function and neuroplasticity following injury. Evidence suggests that glial cells interact extensively with neurons both chemically and physically, reinforcing their role as pivotal for higher brain functions such as learning and memory. Collectively, this mini review surveys investigations of how glial dysfunction following brain injury can alter mechanisms of synaptic plasticity and how this may be related to an increased risk for persistent memory deficits. We also include recent findings, that demonstrate new molecular avenues for clinical biomarker discovery.

Mild blast traumatic brain injury (bTBI) accounts for the majority of brain injury in United States service members and other military personnel worldwide. The mechanisms of primary blast brain injury continue to be disputed with little evidence to support one or a combination of theories. The main hypotheses addressed in this review are blast wave transmission through the skull orifices, direct cranial transmission, skull flexure dynamics, thoracic surge, acceleration, and cavitation. Each possible mechanism is discussed using available literature with the goal of focusing research efforts to address the limitations and challenges that exist in blast injury research. Multiple mechanisms may contribute to the pathology of bTBI and could be dependent on magnitudes and orientation to blast exposure. Further focused biomechanical investigation with cadaver, in vivo, and finite element models would advance our knowledge of bTBI mechanisms. In addition, this understanding could guide future research and contribute to the greater goal of developing relevant injury criteria and mandates to protect our soldiers on the battlefield.

Few preclinical studies have assessed the long-term neuropathology and behavioral deficits after sustaining blast-induced neurotrauma (BINT). Previous studies have shown extensive astrogliosis and cell death at acute stages (<7 days) but the temporal response at a chronic stage has yet to be ascertained. Here, we used behavioral assays, immmunohistochemistry and neurochemistry in limbic areas such as the amygdala (Amy), Hippocampus (Hipp), nucleus accumbens (Nac) and prefrontal cortex (PFC), to determine the long-term effects of a single blast exposure. Behavioral results identified elevated avoidance behavior and decreased short-term memory at either one or three months after a single blast event. At three months after BINT, markers for neurodegeneration (FJB) and microglia activation (Iba-1) increased while index of mature neurons (NeuN) significantly decreased in all brain regions examined. Gliosis (GFAP) increased in all regions except the Nac but only PFC was positive for apoptosis (caspase-3). At three months, tau was selectively elevated in the PFC and Hipp whereas α-synuclein transiently increased in the Hipp at one month after blast exposure. The composite neurochemical measure, myo-inositol+glycine/creatine, was consistently increased in each brain region three months following blast. Overall, a single blast event resulted in enduring long-term effects on behavior and neuropathological sequelae.