Neuroprotective Role of Aminoguanidine in Behavioral Changes after Blast Injury

Moochhala, Shabbir; Shirhan,; Lu, Jia; Teng, C H; Greengrass, Colin

doi:10.1097/01.ta.0000066181.50879.7a

Cited by 76 publications

(63 citation statements)

References 32 publications

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“…52 The studies reported here, which were conducted using general anesthesia, however, suggest that a blast-related mTBI exposure can induce PTSD-related traits independent of exposure to a PTSD stressor. Unlike in some other studies, 5,26,31,33,34,36,38,43,[47][48][49][50] we did not see cognitive effects. No deficits were present in a Morris water maze or in a win-shift task, a relatively challenging test of working memory.…”

Section: Figcontrasting

confidence: 54%

“…33 These studies have documented a variety of, at least, short-term effects, suggesting that blast can be associated with anxiety as well as impairments in a variety of learning and memory tasks. 5,26,31,34,36,43,47,49,50 One study also reported impairments in prepulse inhibition immediately after blast exposure, changes that had mostly recovered by 90 days after exposure. 38 We utilized a rat model of mTBI in which adult male rats were exposed to a controlled blast overpressure injury in a shock tube.…”

Section: Discussionmentioning

confidence: 99%

“…23 Animals have been exposed to various forms of blast ranging from direct exposure to live explosives to controlled blast waves produced by compressed-air generators (reviewed in Elder et al 1 ) with activity in this area increasing dramatically in rodent models in recent years. 5, A number of studies have begun to look at the behavioral effects of blast across a range of blast exposures 5,26,31,33,34,36,38,43,[47][48][49][50] using blast alone or blast in combination with repeated stress 36 or other factors such as transportation or anesthesia. 33 These studies have documented a variety of, at least, short-term effects, suggesting that blast can be associated with anxiety as well as impairments in a variety of learning and memory tasks.…”

Section: Discussionmentioning

confidence: 99%

“…Fewer studies have examined effects of lower-level blasts, such as those studied here, which are likely more comparable to the mTBI exposures that are the most common form of TBI in the current war zones. In addition, in those studies that have utilized lower-level blast exposures, cognitive changes were examined over relatively short time intervals after exposure, 5,43,49,50 unlike the present studies, in which cognitive testing was performed > 2 months after injury. Differentially expressed proteins were identified by 2D gel electrophoresis on pooled samples of posterior and anterior cortex from three blastexposed and three control subjects.…”

Section: Figmentioning

confidence: 99%

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Blast Exposure Induces Post-Traumatic Stress Disorder-Related Traits in a Rat Model of Mild Traumatic Brain Injury

Elder

Dorr²,

Gasperi³

et al. 2012

Journal of Neurotrauma

194

214

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Blast related traumatic brain injury (TBI) has been a major cause of injury in the wars in Iraq and Afghanistan. A striking feature of the mild TBI (mTBI) cases has been the prominent association with post-traumatic stress disorder (PTSD). However, because of the overlapping symptoms, distinction between the two disorders has been difficult. We studied a rat model of mTBI in which adult male rats were exposed to repetitive blast injury while under anesthesia. Blast exposure induced a variety of PTSD-related behavioral traits that were present many months after the blast exposure, including increased anxiety, enhanced contextual fear conditioning, and an altered response in a predator scent assay. We also found elevation in the amygdala of the protein stathmin 1, which is known to influence the generation of fear responses. Because the blast overpressure injuries occurred while animals were under general anesthesia, our results suggest that a blastrelated mTBI exposure can, in the absence of any psychological stressor, induce PTSD-related traits that are chronic and persistent. These studies have implications for understanding the relationship of PTSD to mTBI in the population of veterans returning from the wars in Iraq and Afghanistan.

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Section: Figcontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

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Blast Exposure Induces Post-Traumatic Stress Disorder-Related Traits in a Rat Model of Mild Traumatic Brain Injury

Elder

Dorr²,

Gasperi³

et al. 2012

Journal of Neurotrauma

194

214

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“…The microglial activation was particularly pronounced in the superficial regions of the cerebral and cerebellar cortex. Performance on motor tasks in rats was impaired after exposure to primary blast explosions [24]. These investigators also reported degeneration of neurons in the cerebral cortex.…”

Section: Experimental Animal Studies On Blast-related Brain Injurymentioning

confidence: 74%

Pathology of blast-related brain injury

Kocsis

Tessler²

2009

JRRD

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Abstract-Blasts are responsible for about two-thirds of the combat injuries in Operation Iraqi Freedom and Operation Enduring Freedom, which include at least 1,200 traumatic brain injuries. Blasts inflict damage to the brain directly and by causing injuries to other organs, resulting in air emboli, hypoxia, and shock. Direct injuries to the brain result from rapid shifts in air pressure (primary blast injury), from impacts with munitions fragments and other objects propelled by the explosion (secondary blast injury), and from collisions with objects and rapid acceleration of individuals propelled by the explosion (tertiary blast injury). Tertiary injury can occur from a building or other structure collapsing and from an individual being thrown by the blast wind. The pathological consequences of secondary and tertiary blast injuries are very likely to be similar to those of other types of mechanical trauma seen in civilian life. The damage attributable to the specific effects of a blast, however, has received little study, although it has been assumed to include the focal and diffuse lesions characteristic of closed head injuries. Available clinical studies of blast injuries show focal damage similar to that found in other types of closed head injuries but have not determined whether diffuse axonal injury also occurs. In this article, we will try to reach a better understanding of the specific pathology of blast-related brain injury by reviewing the available experimental studies and the autopsy reports of victims of terrorist attacks and military casualties dating back to World War I.

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Increase in blood–brain barrier permeability, oxidative stress, and activated microglia in a rat model of blast‐induced traumatic brain injury

Readnower

Chavko

Adeeb

et al. 2010

J of Neuroscience Research

250

229

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Traumatic brain injury (TBI) as a consequence of exposure to blast is increasingly prevalent in military populations, with the underlying pathophysiological mechanisms mostly unknown. In the present study, we utilized an air-driven shock tube to investigate the effects of blast exposure (120 kPa) on rat brains. Immediately following exposure to blast neurological function was reduced. BBB permeability was measured using IgG antibody and evaluating its immunoreactivity in the brain. At 3 and 24 h post-exposure there was a transient significant increase in IgG staining in the cortex. At 3 days post-exposure IgG immunoreactivity returned to control levels. Quantitative immunostaining was employed to determine the temporal course of brain oxidative stress following exposure to blast. Levels of 4-hydroxynonenal (4HNE) and 3-nitrotyrosine (3NT) were significantly increased at 3 h post-exposure and returned to control levels at 24 h post-exposure. The response of microglia to blast exposure was determined by autoradiographic localization of 3 H-PK11195 binding. At 5 days post-exposure increased binding was observed in the contralateral and ipsilateral dentate gyrus. These regions also displayed increased binding at 10 days post-exposure; in addition to these regions there was increased binding in the contralateral ventral hippocampus and substantia nigra at this time point. Using antibodies against CD11b/c, microglia morphology characteristic of activated microglia was observed in the hippocampus and substantia nigra of animals exposed to blast. These results indicate that BBB breakdown, oxidative stress, and microglia activation likely play a role in the neuropathology associated with TBI as a result of blast exposure.

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Neuroprotective Role of Aminoguanidine in Behavioral Changes after Blast Injury

Abstract: It is thus suggested that AG could play a neuroprotective role in rats subjected to blast exposure.

Cited by 76 publications

References 32 publications

Blast Exposure Induces Post-Traumatic Stress Disorder-Related Traits in a Rat Model of Mild Traumatic Brain Injury

Blast Exposure Induces Post-Traumatic Stress Disorder-Related Traits in a Rat Model of Mild Traumatic Brain Injury

Pathology of blast-related brain injury

Increase in blood–brain barrier permeability, oxidative stress, and activated microglia in a rat model of blast‐induced traumatic brain injury

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