Jabez Gondokusumo

Introduction: Traumatic brain injury (TBI) results from a violent blow or jolt to the head and can have lasting neurological impacts¹². TBI can be caused by the detonation of an explosive device, which produces a force that acts mechanistically similar to blunt force trauma that damages the brain and other cranial structures.³ Methods: The levels and localization of phosphorylated tau (p-tau) were assessed in brain tissues through western blot and immunostaining to explore the consequences of low-level blast wave exposure in rats.⁴ Next, the role of seizures in the spread of tauopathy was explored using genetically engineered zebrafish that were subjected to pressure waves.⁵ Moreover, biomarkers of injury were identified in a study where blood samples were collected from military personnel participating in a blast-related training program.⁶ To investigate the development of anxiety behaviors, rats were subjected to a series of behavioral tests that assessed their anxiety levels following repetitive low blast wave exposure.^7,8 Lastly, to highlight the long-term effects of blast-induced brain injury, veterans with a history of TBI underwent brain MRI scans, as well as cognitive function testing.⁹ Results: Blast-induced injury in rats resulted in accumulation of p-tau in the brain.⁴ Zebrafish subjected to pressure waves displayed post-traumatic seizure-like behavior.⁵ Furthermore, the intensity of the post-traumatic seizures greatly influenced the progression of tauopathy, and such progression diminished with the application of dynamin inhibitors and anticonvulsants. ⁵Moreover, military personnel subjected to moderate blast exposure developed statistically significant elevated concentrations of neurofilament light chain (NfL) protein, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) compared to the control group.⁴⁶ Additionally, rats subjected to repetitive low-level blasts exhibited reduced movement in the center of the field in an open field test, indicative of anxiety.^7,8 Such anxiety-like behavior persisted 45 days later, a phenomenon known as “blast-induced post-traumatic stress disorder (PTSD)”.^7,8  Lastly, veterans with a history of mild TBI and loss of consciousness displayed greater white matter abnormalities on MRI scans, which correlated with worsening cognitive function.⁹ Conclusions:  The mechanism of blast-induced brain injury involves the development of seizures post-brain injury, which leads to a cascade of tauopathy progression and neuronal damage likely mediated by proinflammatory molecules. Potential biomarkers of brain injury include p-tau in the brain and NfL, IL-6, and TNF-α in the blood. The long-term effects of blast-induced brain injury include the development of blast-induced PTSD and white matter abnormalities, which can lead to lasting cognitive and mood impairments.

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