Pathophysiology of battlefield associated traumatic brain injury

Duckworth, Josh; Grimes, Jamie; Ling, Geoffrey

doi:10.1016/j.pathophys.2012.03.001

Cited by 50 publications

(38 citation statements)

References 47 publications

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“…Spalling has been identified as a leading cause of endothelial injury and activation of microglia (Duckworth et al, 2012), consistent with our findings. Similarly, endothelial damage results in a loss of tight junction integrity and consequently the potential for increased blood-brain barrier permeability and microvascular injury (Duckworth et al, 2012). Notably, increased BBB permeability has been found as late as one month following blastinduced brain injury in a preclinical rodent model, indicating the presence of lasting microvascular dysfunction (Rubovitch et al, 2011).…”

Section: Discussionsupporting

confidence: 92%

“…Spallation refers to the interface-based disruption that occurs between tissues of different densities upon a compression wave in the denser medium reflecting at the interface resulting in displacement and fragmentation of the denser medium into the less dense medium (Cernak and Noble-Haeusslein, 2010;Covey and Born, 2010;Yeh and Schecter, 2012). Spalling has been identified as a leading cause of endothelial injury and activation of microglia (Duckworth et al, 2012), consistent with our findings. Similarly, endothelial damage results in a loss of tight junction integrity and consequently the potential for increased blood-brain barrier permeability and microvascular injury (Duckworth et al, 2012).…”

Section: Discussionsupporting

confidence: 87%

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Modeling clinically relevant blast parameters based on scaling principles produces functional & histological deficits in rats

Turner

Naser

Logsdon

et al. 2013

Experimental Neurology

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 87%

Modeling clinically relevant blast parameters based on scaling principles produces functional & histological deficits in rats

Turner

Naser

Logsdon

et al. 2013

Experimental Neurology

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“…3 Diffuse cerebral edema is a prominent pathophysiologic feature in the acute period of bTBI that contributes to neurologic decline, and is thought to be closely related to cerebrovascular compromise. 2,11,48 These pathological signaling mechanisms may contribute to cognitive and behavioral deficits after blast injury. 1,7,14,49 Despite the fact that BBB breakdown is a transient phenomenon that is repaired within days, barrier compromise may be linked to a number of alternative signaling pathways that can result in long-term pathological effects.…”

Section: Discussionmentioning

confidence: 99%

Time Course and Size of Blood–Brain Barrier Opening in a Mouse Model of Blast-Induced Traumatic Brain Injury

Hue

Cho

Cao

et al. 2016

Journal of Neurotrauma

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An increasing number of studies have reported blood-brain barrier (BBB) dysfunction after blast-induced traumatic brain injury (bTBI). Despite this evidence, there is limited quantitative understanding of the extent of BBB opening and the time course of damage after blast injury. In addition, many studies do not report kinematic parameters of head motion, making it difficult to separate contributions of primary and tertiary blast-loading. Detailed characterization of blast-induced BBB damage may hold important implications for serum constituents that may potentially cross the compromised barrier and contribute to neurotoxicity, neuroinflammation, and persistent neurologic deficits. Using an in vivo bTBI model, systemic administration of sodium fluorescein (NaFl; 376 Da), Evans blue (EB; 69 kDa when bound to serum albumin), and dextrans (3-500 kDa) was used to estimate the pore size of BBB opening and the time required for recovery. Exposure to blast with 272 ± 6 kPa peak overpressure, 0.69 ± 0.01 ms duration, and 65 ± 1 kPa*ms impulse resulted in significant acute extravasation of NaFl, 3 kDa dextran, and EB. However, there was no significant acute extravasation of 70 kDa or 500 kDa dextrans, and minimal to no extravasation of NaFl, dextrans, or EB 1 day after exposure. This study presents a detailed analysis of the time course and pore size of BBB opening after bTBI, supported by a characterization of kinematic parameters associated with blast-induced head motion.

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“…3 Due to the complexity and unique physical forces responsible for blast-induced TBI, it is now widely believed that the TBI resulting from blast exposure is relatively distinct from other closed head or penetrating brain injuries. 4 The primary, secondary, tertiary, and quaternary injury phases of blast exposure are believed to contribute to the multifaceted mechanisms involved in blast TBI. Although several clinical and animal studies have explored the biochemical/histopathological changes and behavioral deficits resulting from blast exposure, 3,5-11 the complex biochemical and molecular mechanisms of blast TBI and how it triggers subsequent secondary pathological processes and long-term neurobehavioral abnormalities are still not well understood.…”

Section: Introductionmentioning

confidence: 99%

Acute Mitochondrial Dysfunction after Blast Exposure: Potential Role of Mitochondrial Glutamate Oxaloacetate Transaminase

Arun

Abu-Taleb

Oguntayo

et al. 2013

Journal of Neurotrauma

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Use of improvised explosive devices has significantly increased the incidence of traumatic brain injury (TBI) and associated neuropsychiatric deficits in the recent wars in Iraq and Afghanistan. Acute deleterious effects of single and repeated blast exposure can lead to long-term neurobiological effects and neuropsychiatric deficits. Using in vitro and in vivo shock tube models of blast-induced TBI, we studied changes in mitochondrial energy metabolism after blast exposure. Single and repeated blast exposures in vitro resulted in significant decreases in neuronal adenosine triphosphate (ATP) levels at 6 h post-blast that returned towards normal levels by 24 h. Similar changes in ATP also were observed in the cerebral cortices of mice subjected to single and repeated blast exposures. In neurons, mitochondrial glutamate oxaloacetate transaminase (GOT2) plays a critical role in metabolism and energy production. Proteomic analysis of brain cortices showed a significant decrease in GOT2 levels 6 h after repeated blast exposures, which was further confirmed by Western blotting. Western blot analysis of GOT2 and pyruvate dehydrogenase in the cortex showed direct correlation only between GOT2 and ATP levels. Activity of GOT2 in the isolated cortical mitochondria also showed significant decrease at 6 h supporting the results of proteomic and Western blot analyses. Knowing the significant role of GOT2 in the neuronal mitochondrial energy metabolism, it is quite likely that the down regulation of GOT2 after blast exposure is playing a significant role in mitochondrial dysfunction after blast exposure.

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Pathophysiology of battlefield associated traumatic brain injury

Cited by 50 publications

References 47 publications

Modeling clinically relevant blast parameters based on scaling principles produces functional & histological deficits in rats

Modeling clinically relevant blast parameters based on scaling principles produces functional & histological deficits in rats

Time Course and Size of Blood–Brain Barrier Opening in a Mouse Model of Blast-Induced Traumatic Brain Injury

Acute Mitochondrial Dysfunction after Blast Exposure: Potential Role of Mitochondrial Glutamate Oxaloacetate Transaminase

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