Low-Level Primary Blast Induces Neuroinflammation and Neurodegeneration in Rats

• Published in: Military medicine Vol. 184; no. Supplement_1; pp. 265 - 272
• Main Authors: Li, Yansong, Yang, Zhangsheng, Liu, Bin, Valdez, Celina, Chavko, Mikulas, Cancio, Leopoldo C
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-03-2019
• Subjects: Animals; Biomarkers - analysis; Brain Injuries, Traumatic - etiology; Brain Injuries, Traumatic - pathology; Casualties; Chemokine CCL5 - analysis; Chemokine CXCL1 - analysis; Chemokines - analysis; Cytokines; Cytokines - analysis; Disease Models, Animal; Encephalitis - enzymology; Encephalitis - etiology; Encephalitis - pathology; Explosions - statistics & numerical data; Interleukin-12 - analysis; Interleukin-18 - analysis; Interleukin-1beta - analysis; Interleukin-6 - analysis; Nerve Degeneration - enzymology; Nerve Degeneration - etiology; Nerve Degeneration - pathology; Neurodegeneration; Rats - injuries; Traumatic brain injury; Tumor Necrosis Factor-alpha - analysis; neurodegeneration; traumatic brain injury; mild blast injury; neuroinflammation
• ISSN: 0026-4075; 1930-613X
• DOI: 10.1093/milmed/usy330

Abstract
Objective
Mild blast traumatic brain injury is commonly prevalent in modern combat casualty care and has been associated with the development of neurodegenerative conditions. However, whether primary lower level blast overpressure (LBOP) causes neurodegeneration and neuroinflammation remains largely unknown. The aim of our present study was to determine whether LBOP can cause neuroinflammation and neurodegeneration.
Methods
Anesthetized rats were randomly assigned to LBOP group (70 kPa, n = 5) or sham group (without blast, n = 5). Histopathological and cytokine changes in brain tissue at 5 days post-injury were evaluated by hematoxylin-eosin staining and Bioplex assay, respectively.
Results
Histopathological assessment revealed neuronal degeneration and increased density of inflammatory cells in frontal and parietal cortex, hippocampus and thalamus in rats exposed to LBOP. LBOP exposure significantly elevated levels of pro-inflammatory cytokines (EPO, IL-1β, IL-6, IL-12, IL-18, and TNF-α) and chemokines (GRO and RANTES) as well as of an anti-inflammatory cytokine (IL-13) in the frontal cortex.
Conclusions
This study reveals a role of neuroinflammation in neurodegeneration after mild blast traumatic brain injury. Therapies that target this process might in warfighters might function either by attenuating the development of post-traumatic stress disorder, chronic traumatic encephalopathy and Alzheimer’s disease, or by slowing their progression.