Exposure to mild blast forces induces neuropathological effects, neurophysiological deficits and biochemical changes
Authors:
- Adan HernandezAHAdan Hernandez
- Chunfeng TanCTChunfeng Tan
- Florian PlattnerFPFlorian Plattner
- Aric F. LogsdonALAric F. Logsdon
- Karine PozoKPKarine Pozo
- Mohammad A. YousufMYMohammad A. Yousuf
- Tanvir SinghTSTanvir Singh
- Ryan C. TurnerRTRyan C. Turner
- Brandon P. Lucke-WoldBrandon P. Lucke-Wold
- Jason D. HuberJHJason D. Huber
- Charles L. RosenCRCharles L. Rosen
- James A. BibbJBJames A. Bibb
Open Access
- 9 November 2018
- journal article
- research article
- Published by Springer Nature in Molecular Brain
- Vol. 11 (1) , 64
Abstract
Direct or indirect exposure to an explosion can induce traumatic brain injury (TBI) of various severity levels. Primary TBI from blast exposure is commonly characterized by internal injuries, such as vascular damage, neuronal injury, and contusion, without external injuries. Current animal models of blast-induced TBI (bTBI) have helped to understand the deleterious effects of moderate to severe blast forces. However, the neurological effects of mild blast forces remain poorly characterized. Here, we investigated the effects caused by mild blast forces combining neuropathological, histological, biochemical and neurophysiological analysis. For this purpose, we employed a rodent blast TBI model with blast forces below the level that causes macroscopic neuropathological changes. We found that mild blast forces induced neuroinflammation in cerebral cortex, striatum and hippocampus. Moreover, mild blast triggered microvascular damage and axonal injury. Furthermore, mild blast caused deficits in hippocampal short-term plasticity and synaptic excitability, but no impairments in long-term potentiation. Finally, mild blast exposure induced proteolytic cleavage of spectrin and the cyclin-dependent kinase 5 activator, p35 in hippocampus. Together, these findings show that mild blast forces can cause aberrant neurological changes that critically impact neuronal functions. These results are consistent with the idea that mild blast forces may induce subclinical pathophysiological changes that may contribute to neurological and psychiatric disorders.Keywords
Funding Information
- National Institute of Mental Health (MH083711)
- National Institute on Drug Abuse (DA033485)
- National Institute of Neurological Disorders and Stroke (NS073855)
- Darrell K Royal Fund for Alzheimer's Disease (n/A)
- American Foundation for Pharmaceutical Education (n/a, n/a)
- American Association for Pharmaceutical Scientists (n/a)
This publication has 46 references indexed in Scilit:
- Controlled Low-Pressure Blast-Wave Exposure Causes Distinct Behavioral and Morphological Responses Modelling Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Comorbid Mild Traumatic Brain Injury–Post-Traumatic Stress DisorderJournal of Neurotrauma, 2017
- Diffuse axonal injury in brain trauma: insights from alterations in neurofilamentsFrontiers in Cellular Neuroscience, 2014
- A time course of NADPH-oxidase up-regulation and endothelial nitric oxide synthase activation in the hippocampus following neurotraumaFree Radical Biology and Medicine, 2014
- Blast Exposure Induces Post-Traumatic Stress Disorder-Related Traits in a Rat Model of Mild Traumatic Brain InjuryJournal of Neurotrauma, 2012
- Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse ModelScience Translational Medicine, 2012
- A mouse model of blast-induced mild traumatic brain injuryExperimental Neurology, 2011
- Characteristics of an Explosive Blast-Induced Brain Injury in an Experimental ModelJournal of Neuropathology & Experimental Neurology, 2011
- Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degenerationBrain Research, 2000
- Enduring suppression of hippocampal long-term potentiation following traumatic brain injury in ratBrain Research, 1992
- Immunoperoxidase staining of formalin-fixed, paraffin-embedded, human renal biopsies with a comparison of the peroxidase-antiperoxidase (PAP) and indirect methods.Journal of Clinical Pathology, 1981