Repeated Low-Level Blast Overpressure Leads to Endovascular Disruption and Alterations in TDP-43 and Piezo2 in a Rat Model of Blast TBI.

摘要: Recent evidence linking repeated low-level blast overpressure exposure in operational and training environments with neurocognitive decline, neuroinflammation, neurodegenerative processes has prompted concern over the cumulative deleterious effects of on brains service members. Repetitive to primary may cause symptoms (subclinical) similar those seen mild traumatic brain injury (TBI), progressive vascular cellular changes, which could contribute neurodegeneration. At level, mechanical force associated can perturbations brain, leading secondary injury. To examine repetitive an advanced simulator (ABS) was used closely mimic "free-field" blast. Rats were exposed 1-4 daily blasts (one per day, separated by 24 h) at 13, 16, or 19 psi peak incident pressures a positive duration 4-5 ms, either transverse longitudinal orientation. Blood-brain barrier (BBB) markers (vascular endothelial growth factor (VEGF), occludin, claudin-5), transactive response DNA binding protein (TDP-43), mechanosensitive channel Piezo2 measured following exposure. Changes expression VEGF, claudin-5 after indicate alterations BBB, been shown be disrupted TBI. TDP-43 is very tightly regulated altered found clinically-diagnosed TBI patients. levels differentially affected number magnitude exposures, decreasing 2 but increasing greater exposures various intensities. Lastly, dysregulated here observed increase multiple moderate magnitude, indicating that change sensitivity stimuli These findings reveal lead pathophysiological changes demonstrating possible link between disease, important first step understanding how prevent these diseases soldiers