Differential effects on TDP-43, piezo-2, tight-junction proteins in various brain regions following repetitive low-intensity blast overpressure

Frontiers in Neurology

Neurology

Lanier Heyburn¹  Rodrigo Urioste¹  Venkatasivasai Sujith Sajja¹  Donna Wilder¹  Andrew Batuure¹  Joseph B. Long¹  Shataakshi Dahal²  Rania Abutarboush³  Eileen Reed³  Stephen T. Ahlers³ 

[1] Blast Induced Neurotrauma Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States;Blast Induced Neurotrauma Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States;The Geneva Foundation, Tacoma, WA, United States;Naval Medical Research Center, Silver Spring, MD, United States;

关键词: relBOP;    blast;    TDP-43;    piezo;    tight junction proteins;   

DOI  :  10.3389/fneur.2023.1237647

 received in 2023-06-12, accepted in 2023-09-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionMild traumatic brain injury (mTBI) caused by repetitive low-intensity blast overpressure (relBOP) in military personnel exposed to breaching and heavy weapons is often unrecognized and is understudied. Exposure to relBOP poses the risk of developing abnormal behavioral and psychological changes such as altered cognitive function, anxiety, and depression, all of which can severely compromise the quality of the life of the affected individual. Due to the structural and anatomical heterogeneity of the brain, understanding the potentially varied effects of relBOP in different regions of the brain could lend insights into the risks from exposures.MethodsIn this study, using a rodent model of relBOP and western blotting for protein expression we showed the differential expression of various neuropathological proteins like TDP-43, tight junction proteins (claudin-5, occludin, and glial fibrillary acidic protein (GFAP)) and a mechanosensitive protein (piezo-2) in different regions of the brain at different intensities and frequency of blast.ResultsOur key results include (i) significant increase in claudin-5 after 1x blast of 6.5 psi in all three regions and no definitive pattern with higher number of blasts, (ii) significant increase in piezo-2 at 1x followed by significant decrease after multiple blasts in the cortex, (iii) significant increase in piezo-2 with increasing number of blasts in frontal cortex and mixed pattern of expression in hippocampus and (iv) mixed pattern of TDP-3 and GFAP expression in all the regions of brain.DiscussionThese results suggest that there are not definitive patterns of changes in these marker proteins with increase in intensity and/or frequency of blast exposure in any particular region; the changes in expression of these proteins are different among the regions. We also found that the orientation of blast exposure (e.g. front vs. side exposure) affects the altered expression of these proteins.

【 授权许可】

Unknown   
Copyright © 2023 Heyburn, Dahal, Abutarboush, Reed, Urioste, Batuure, Wilder, Ahlers, Long and Sajja.