Blast-Related Mild TBI Alters Anxiety-Like Behavior and Transcriptional Signatures in the Rat Amygdala

Blaze, Jennifer; Choi, InBae; Wang, Zhaoyu; Umali, Michelle; Mendelev, Natalia; Tschiffely, Anna E.; Ahlers, Stephen T.; Elder, Gregory A.; Ge, Yongchao; Haghighi, Fatemeh

doi:10.3389/fnbeh.2020.00160

Cited by 23 publications

(17 citation statements)

References 66 publications

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“…This may be indicative of increased communication within amygdala circuitry following blast injury ( Ratliff et al, 2019 ). Repeated mild blast TBI has shown alterations in the transcriptome within the BLA and CeA subregions which were associated with anxiety-like behaviors ( Blaze et al, 2020 ), and single blast injury has led to a decrease in the number of BLA pyramidal neurons ( Heldt et al, 2014 ). An impairment in inhibitory transmission in the BLA following mild TBI as indicated by a decrease in GABAergic neurons has also been reported ( Almeida-Suhett et al, 2014 ) as well as decreased network excitability in the amygdala ( Palmer et al, 2016 ).…”

Section: Animal Studiesmentioning

confidence: 99%

A Role for the Amygdala in Impairments of Affective Behaviors Following Mild Traumatic Brain Injury

McCorkle

Barson

Raghupathi

2021

Front. Behav. Neurosci.

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Mild traumatic brain injury (TBI) results in chronic affective disorders such as depression, anxiety, and fear that persist up to years following injury and significantly impair the quality of life for patients. Although a great deal of research has contributed to defining symptoms of mild TBI, there are no adequate drug therapies for brain-injured individuals. Preclinical studies have modeled these deficits in affective behaviors post-injury to understand the underlying mechanisms with a view to developing appropriate treatment strategies. These studies have also unveiled sex differences that contribute to the varying phenotypes associated with each behavior. Although clinical and preclinical studies have viewed these behavioral deficits as separate entities with unique neurobiological mechanisms, mechanistic similarities suggest that a novel approach is needed to advance research on drug therapy. This review will discuss the circuitry involved in the expression of deficits in affective behaviors following mild TBI in humans and animals and provide evidence that the manifestation of impairment in these behaviors stems from an amygdala-dependent emotional processing deficit. It will highlight mechanistic similarities between these different types of affective behaviors that can potentially advance mild TBI drug therapy by investigating treatments for the deficits in affective behaviors as one entity, requiring the same treatment.

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Section: Animal Studiesmentioning

confidence: 99%

A Role for the Amygdala in Impairments of Affective Behaviors Following Mild Traumatic Brain Injury

McCorkle

Barson

Raghupathi

2021

Front. Behav. Neurosci.

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“…Perez-Garcia et al (38) showed for the same rat model that the blast-exposed rats spent more time in the closed arms even at 29-30 weeks after exposure. Furthermore, Blaze et al (39) observed an anxietylike phenotype for the same rat model at 1-1.5 months postinjury, but it was diminished by 12-13 months post-injury. The present results on elevated plus maze test can be featured by the fact that the increased rat anxiety appeared in the acute phase (7 days post-exposure).…”

Section: Discussionmentioning

confidence: 94%

“…These behavioral changes were shown to be correlated with decreased axonal densities in CB and CC. Some studies reported the results of anxiety tests using an elevated plus maze or elevated zero maze test for rats exposed to blast overpressures (35)(36)(37)(38)(39). Kovesdi et al (35) reported that the time spent in open arms was not significantly decreased in rats at 9 days post-exposure, while it was significantly reduced (anxiety increased) in rats after 46 days in experiments using a shock tube (∼20 psi [∼138 kPa], single exposure).…”

Section: Discussionmentioning

confidence: 99%

Behavioral and Histopathological Impairments Caused by Topical Exposure of the Rat Brain to Mild-Impulse Laser-Induced Shock Waves: Impulse Dependency

et al. 2021

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Although an enormous number of animal studies on blast-induced traumatic brain injury (bTBI) have been conducted, there still remain many uncertain issues in its neuropathology and mechanisms. This is partially due to the complex and hence difficult experimental environment settings, e.g., to minimize the effects of blast winds (tertiary mechanism) and to separate the effects of brain exposure and torso exposure. Since a laser-induced shock wave (LISW) is free from dynamic pressure and its energy is spatially well confined, the effects of pure shock wave exposure (primary mechanism) solely on the brain can be examined by using an LISW. In this study, we applied a set of four LISWs in the impulse range of 15–71 Pa·s to the rat brain through the intact scalp and skull; the interval between each exposure was ~5 s. For the rats, we conducted locomotor activity, elevated plus maze and forced swimming tests. Axonal injury in the brain was also examined by histological analysis using Bodian silver staining. Only the rats with exposure at higher impulses of 54 and 71 Pa·s showed significantly lower spontaneous movements at 1 and 2 days post-exposure by the locomotor activity test, but after 3 days post-exposure, they had recovered. At 7 days post-exposure, however, these rats (54 and 71 Pa·s) showed significantly higher levels of anxiety-related and depression-like behaviors by the elevated plus maze test and forced swimming test, respectively. To the best of the authors' knowledge, there have been few studies in which a rat model showed both anxiety-related and depression-like behaviors caused by blast or shock wave exposure. At that time point (7 days post-exposure), histological analysis showed significant decreases in axonal density in the cingulum bundle and corpus callosum in impulse-dependent manners; axons in the cingulum bundle were found to be more affected by a shock wave. Correlation analysis showed a statistically significant correlation between the depression like-behavior and axonal density reduction in the cingulum bundle. The results demonstrated the dependence of behavior deficits and axonal injury on the shock wave impulse loaded on the brain.

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“…Many veterans from the recent conflicts in Iraq and Afghanistan suffer from chronic neurobehavioral syndromes that include post-traumatic stress disorder (PTSD) [ 31 ]. Indeed, a striking feature in veterans from the most recent war theaters has been the overlap between a history of blast-related mild TBI (mTBI) and PTSD [ 17 , 31 , 115 , 134 , 140 , 141 ]. While these symptoms may improve, they frequently persist and may worsen with declines driven mainly by worsening PTSD and depression [ 83 ].…”

Section: Introductionmentioning

confidence: 99%

Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation

Sosa

Gasperi

Pryor

et al. 2021

acta neuropathol commun

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Cerebral vascular injury as a consequence of blast-induced traumatic brain injury is primarily the result of blast wave-induced mechanical disruptions within the neurovascular unit. In rodent models of blast-induced traumatic brain injury, chronic vascular degenerative processes are associated with the development of an age-dependent post-traumatic stress disorder-like phenotype. To investigate the evolution of blast-induced chronic vascular degenerative changes, Long-Evans rats were blast-exposed (3 × 74.5 kPa) and their brains analyzed at different times post-exposure by X-ray microcomputed tomography, immunohistochemistry and electron microscopy. On microcomputed tomography scans, regional cerebral vascular attenuation or occlusion was observed as early as 48 h post-blast, and cerebral vascular disorganization was visible at 6 weeks and more accentuated at 13 months post-blast. Progression of the late-onset pathology was characterized by detachment of the endothelial and smooth muscle cellular elements from the neuropil due to degeneration and loss of arteriolar perivascular astrocytes. Development of this pathology was associated with vascular remodeling and neuroinflammation as increased levels of matrix metalloproteinases (MMP-2 and MMP-9), collagen type IV loss, and microglial activation were observed in the affected vasculature. Blast-induced chronic alterations within the neurovascular unit should affect cerebral blood circulation, glymphatic flow and intramural periarterial drainage, all of which may contribute to development of the blast-induced behavioral phenotype. Our results also identify astrocytic degeneration as a potential target for the development of therapies to treat blast-induced brain injury.

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Blast-Related Mild TBI Alters Anxiety-Like Behavior and Transcriptional Signatures in the Rat Amygdala

Cited by 23 publications

References 66 publications

A Role for the Amygdala in Impairments of Affective Behaviors Following Mild Traumatic Brain Injury

A Role for the Amygdala in Impairments of Affective Behaviors Following Mild Traumatic Brain Injury

Behavioral and Histopathological Impairments Caused by Topical Exposure of the Rat Brain to Mild-Impulse Laser-Induced Shock Waves: Impulse Dependency

Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation

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