Altering endoplasmic reticulum stress in a model of blast-induced traumatic brain injury controls cellular fate and ameliorates neuropsychiatric symptoms.

Neuronal injury following blast-induced traumatic brain injury (bTBI) increases the risk for neuropsychiatric disorders, yet the pathophysiology remains poorly understood. Blood-brain-barrier (BBB) disruption, endoplasmic reticulum (ER) stress, and apoptosis have all been implicated in bTBI. Microvessel compromise is a primary effect of bTBI and is postulated to cause subcellular secondary effects such as ER stress.

Disparity among neural injury models and the unfolded protein response.

Endoplasmic reticulum stress is activated following both stroke and traumatic brain injury producing reactive oxgygen species, increasing intracellular calcium levels, and inducing inflammation; however, the timing and duration of activation varies between injuries. Preventing the immediate effects of ischemic/reperfusion injury or traumatic brain injury is challenging due to short onset of injury, but mitigating the secondary effects is a therapeutically targetable option. Preventative therapies using pharmacological agents have been utilized in pre-clinical models of neural injury to ameliorate secondary effects such as apoptosis and neurodegeneration.

Linking traumatic brain injury to chronic traumatic encephalopathy: identification of potential mechanisms leading to neurofibrillary tangle development.

Significant attention has recently been drawn to the potential link between head trauma and the development of neurodegenerative disease, namely chronic traumatic encephalopathy (CTE). The acute neurotrauma associated with sports-related concussions in athletes and blast-induced traumatic brain injury in soldiers elevates the risk for future development of chronic neurodegenerative diseases such as CTE. CTE is a progressive disease distinguished by characteristic tau neurofibrillary tangles (NFTs) and, occasionally, transactive response DNA binding protein 43 (TDP43) oligomers, both of which have a predilection for perivascular and subcortical areas near reactive astrocytes and microglia.