Exposure to mild blast forces cause brain pathology and deficits

Mild blast forces cause brain pathology and deficits

Hernandez, Adan, et al. Molecular Brain, vol. 11, no. 1, Sept. 2018, doi:10.1186/s13041-018-0408-1.

As many as 300,000 United States service members deployed to Iraq and Afghanistan since 2001 have suffered traumatic brain injury due to explosions. The vast majority of these blast-induced traumatic brain injuries, or bTBIs, were classified as mild.

Unlike severe or moderate bTBIs, a mild bTBI shows no overt brain injury, such as bleeding, hematomas or bruising, and people with a mild bTBI do not lose consciousness or show concussion symptoms. Nevertheless, these injuries can eventually lead to cognitive impairment, loss of attentional function, drug addiction, and anxiety or depressive disorders.

Using a rat model of bTBI, University of Alabama at Birmingham researcher James Bibb, Ph.D., and colleagues show how even mild exposure to a single blast shock wave is able to induce small but potentially very meaningful pathogenic effects that accumulate with time.

These effects, detected at the microscopic level, included microvascular damage, injury to nerve axons and signs of neuroinflammation in various brain regions. Brain function also changed, as shown by impaired short-term synaptic plasticity. The single mild blast also activated biochemical pathways that are associated with stroke and neurodegenerative diseases, including Alzheimer's. These included cleavage of a protein called spectrin that helps form the cytoskeleton of neurons and other cells.

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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.

Posted on BrainLine December 18, 2018.