Blast TBI Models, Neuropathology, and Implications for Seizure Risk

Abstract

Traumatic brain injury (TBI) due to explosive blast exposure is a leading combat casualty. It is also implicated as a key contributor to war related mental health diseases. A clinically important consequence of all types of TBI is a high risk for development of seizures and epilepsy. Seizures have been reported in patients who have suffered blast injuries in the Global War on Terror but the exact prevalence is unknown. The occurrence of seizures supports the contention that explosive blast leads to both cellular and structural brain pathology. Unfortunately, the exact mechanism by which explosions cause brain injury is unclear, which complicates development of meaningful therapies and mitigation strategies. To help improve understanding, detailed neuropathological analysis is needed. For this, histopathological techniques are extremely valuable and indispensable. In the following we will review the pathological results, including those from immunohistochemical and special staining approaches, from recent preclinical explosive blast studies.

Traumatic Brain Injury Research in Military Populations

“…In summary, it was found that a single blast exposure was sufficient to cause brain pathology and memory impairment. This finding replicates the findings of Kovesdi and colleagues, conducted in an F344 rat model (Kovesdi et al, 2011).…”

“…The sequela of bTBI can be temporary or chronic. Posttraumatic epilepsy (PTE) may also develop in 10%-25% of closed head TBI cases and in 50% of those with a penetrating head injury (Kovacs et al, 2014). The risk for developing PTE is correlated to the severity of TBI.…”

“…Since 2000 and the "Global War on Terror," 307,283 soldiers and military personnel have suffered TBI, and 208,952 or 68% of these cases were blast related (Kovacs, Leonessa, & Ling, 2014;Ling, Bandak, Armonda, Grant, & Ecklund, 2009;Okie, 2005). Current statistics on TBI in the U.S. military is available at the Defense and Veterans Brain Injury Center (http://dvbic.dcoe.mil/dod-worldwide-numbers-tbi), and overall casualties are compiled by the Department of Defense' s casualty website (www.defense .gov/news/casualty.pdf).…”

A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

“…[102][103][104] The observed microglial activation is likely to have occurred via their Toll-like 4 receptors in response to small soluble factors (e.g., glutamate, ATP) and/or debris (e.g., cytoskeletal elements, proteolytic breakdown products, and lipid) released by or associated with damaged axons, their terminals, and the associated myelin. 105,106 Many authors have suggested that persistent microglial activation initiates an inflammatory cascade that worsens the outcome after TBI.…”

Adoption of the Transport and Burgers' Equations in Modeling Neurological Shock-Waves in the Human Brain Due to Improvised Explosive Devices (IEDs)

“…Because TBI results from the exposure of military personnel to explosive detonations during modern warfare [5][6][7][8][9]-largely due to IEDs-there is a considerable need for further research in this area. This is to explain, and ultimately mitigate against, the negative consequences of harmful brain trauma, as well as possible mental and psychological disorders that often result.…”