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

Lanier Heyburn; Shataakshi Dahal; Rania Abutarboush; Eileen Reed; Rodrigo Urioste; Andrew Batuure; Donna Wilder; Stephen T Ahlers; Joseph B Long; Venkatasivasai Sujith Sajja

doi:10.3389/fneur.2023.1237647

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

Front Neurol. 2023 Oct 9:14:1237647. doi: 10.3389/fneur.2023.1237647. eCollection 2023.

Affiliations

¹ Blast Induced Neurotrauma Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States.
² The Geneva Foundation, Tacoma, WA, United States.
³ Naval Medical Research Center, Silver Spring, MD, United States.

Abstract

Introduction: Mild 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.

Methods: In 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.

Results: Our 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.

Discussion: These 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.

Keywords: TDP-43; blast; piezo; relBOP; tight junction proteins.