Mild traumatic brain injury in the rat alters neuronal number in the limbic system and increases conditioned fear and anxiety-like behaviors

Meyer, Danielle; Davies, D. R.; Barr, Jeffrey L.; Manzerra, Pasquale; Forster, Gina L.

doi:10.1016/j.expneurol.2012.03.012

Cited by 81 publications

(110 citation statements)

References 78 publications

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“…We, therefore, conclude that BOP did not delay or facilitate extinction to a conditioned fear, although it did alter the magnitude of its expression. This result is consistent with a previous study (Meyer, et al, 2012) that showed that mTBI from weight drop did not alter extinction of a conditioned fear, while altering (in this case increasing) the initial expression of the conditioned fear. The finding is relevant to understanding the relationship between mTBI and PTSD since the persistence of an emotional response to previously neutral stimuli that have been associated with trauma is an integral feature of some PTSD symptoms (American Psychiatric Association, 2000).…”

Section: Discussionsupporting

confidence: 93%

“…showing that mTBI produced an exaggerated conditioned fear as compared to controls (Elder, et al, 2012;Meyer, et al, 2012;Reger, et al, 2012). A major difference between the former studies and the present study is that the conditioned fear in the present study was established (and presumably consolidated into long-term memory) before the mTBI exposures.…”

Section: Discussioncontrasting

confidence: 72%

“…The behavioral changes included decreased exploratory activity on an elevated plus maze, decreased open-field center activity following exposure to a predator cue, enhanced acoustic startle response and an enhanced conditioned fear. mTBI from a weight drop procedure has also been reported to decrease open-arm time in a plus maze without decreasing total distance (six days post injury) and to enhance a conditioned fear (eight days post injury), while 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 7 not affecting its extinction (Meyer, et al, 2012). Thus, evidence exists that mTBI can alter the conditioned fear process.…”

Section: Introductionmentioning

confidence: 99%

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Neurocognitive and Biomarker Evaluation of Combination mTBI from Blast Overpressure and Traumatic Stress

Genovese¹

2013

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY)September 2013 (From -To) 1 September 2012 -31 August 2013 REPORT TYPE Annual DATES COVERED TITLE AND SUBTITLENeurocognitive and Biomarker Evaluation of Combination mTBI from Blast Overpressure and Traumatic Stress 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-10-2-0091 5c. PROGRAM ELEMENT NUMBER AUTHOR(S)Raymond Genovese E-Mail: cpfortmiller@genevusa.org 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)The Geneva Foundation Lakewood, WA 96499 PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S ACRONYM(S) SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTMild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) are major medical issues for the Warfighter. The current project is designed to evaluate the impact of mild traumatic brain injury (using blast overpressure) and the processes involved in traumatic stress (using a predator exposure procedure and a conditioned fear procedure) in a rodent model. The studies evaluate these insults alone and in combination to specifically address the question of whether mTBI can exacerbate the effects of psychological stress. Additionally, following the insults, a molecular biological evaluation is performed based upon the discovery of biomarkers that have been shown to be correlated with other forms of TBI. Thus, the project aims to systematically assess the combined effects of blast overpressure, traumatic stress and learned stress responses in rodents with the aim of understanding how these forces may interact to impact behavior as well as evaluating their outcome on known biomarkers involved in TBI and stress response system activation. SUBJECT TERMSNone provided. Mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) are medical issues for the war fighter. Sometimes, mTBI and PTSD present a convergence of symptoms, ma...

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Section: Discussionsupporting

confidence: 93%

Section: Discussioncontrasting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

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Neurocognitive and Biomarker Evaluation of Combination mTBI from Blast Overpressure and Traumatic Stress

Genovese¹

2013

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“…13 Moreover, our results on amygdala structural changes after diffuse TBI through midline FPI add to the growing literature on the effects of TBI on anxiety-like and fear behavior in models of blast TBI [46][47][48] and weight drop. 49 Important to note, the BLA consists of multiple subpopulations of pyramidal neurons, which may play differential functional roles in fear expression and inhibition. 50,51 However, whether TBI would affect dendritic branching differently across these distinct functional subtypes of glutamatergic neurons remains unknown and is an objective for future research.…”

Section: Discussionmentioning

confidence: 99%

Early and Persistent Dendritic Hypertrophy in the Basolateral Amygdala following Experimental Diffuse Traumatic Brain Injury

Hoffman

Paode

May

et al. 2017

Journal of Neurotrauma

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In the pathophysiology of traumatic brain injury (TBI), the amygdala remains understudied, despite involvement in processing emotional and stressful stimuli associated with anxiety disorders, such as post-traumatic stress disorder (PTSD). Because the basolateral amygdala (BLA) integrates inputs from sensory and other limbic structures coordinating emotional learning and memory, injury-induced changes in circuitry may contribute to psychiatric sequelae of TBI. This study quantified temporal changes in dendritic complexity of BLA neurons after experimental diffuse TBI, modeled by midline fluid percussion injury. At post-injury days (PIDs) 1, 7, and 28, brain tissue from sham and brain-injured adult, male rats was processed for Golgi, glial fibrillary acidic protein (GFAP), or silver stain and analyzed to quantify BLA dendritic branch intersections, activated astrocytes, and regional neuropathology, respectively. Compared to sham, braininjured rats at all PIDs showed enhanced dendritic branch intersections in both pyramidal and stellate BLA neuronal types, as evidenced by Sholl analysis. GFAP staining in the BLA was significantly increased at PID1 and 7 in comparison to sham. However, the BLA was relatively spared from neuropathology, demonstrated by an absence of argyrophilic accumulation over time, in contrast to other brain regions. These data suggest an early and persistent enhancement of dendritic complexity within the BLA after a single diffuse TBI. Increased dendritic complexity would alter information processing into and through the amygdala, contributing to emotional symptoms post-TBI, including PTSD.

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“…35,[37][38][39][133][134][135][136]138,139,[141][142][143][144][145][146][147][148] For example, rotarod deficits and axon injury have been reported after weightdrop TBI. 141,149 A more detailed review of functional deficits and brain pathology after TBI created by impact or weight drop on a closed skull has been provided by others.…”

Section: Comparison With Blast Models In Rodentsmentioning

confidence: 99%

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

Guley

Rogers

Mar

et al. 2016

Journal of Neurotrauma

104

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Mild traumatic brain injury (TBI) from focal head impact is the most common form of TBI in humans. Animal models, however, typically use direct impact to the exposed dura or skull, or blast to the entire head. We present a detailed characterization of a novel overpressure blast system to create focal closed-head mild TBI in mice. A high-pressure air pulse limited to a 7.5 mm diameter area on the left side of the head overlying the forebrain is delivered to anesthetized mice. The mouse eyes and ears are shielded, and its head and body are cushioned to minimize movement. This approach creates mild TBI by a pressure wave that acts on the brain, with minimal accompanying head acceleration-deceleration. A single 20-psi blast yields no functional deficits or brain injury, while a single 25-40 psi blast yields only slight motor deficits and brain damage. By contrast, a single 50-60 psi blast produces significant visual, motor, and neuropsychiatric impairments and axonal damage and microglial activation in major fiber tracts, but no contusive brain injury. This model thus reproduces the widespread axonal injury and functional impairments characteristic of closed-head mild TBI, without the complications of systemic or ocular blast effects or head acceleration that typically occur in other blast or impact models of closed-skull mild TBI. Accordingly, our model provides a simple way to examine the biomechanics, pathophysiology, and functional deficits that result from TBI and can serve as a reliable platform for testing therapies that reduce brain pathology and deficits.

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Mild traumatic brain injury in the rat alters neuronal number in the limbic system and increases conditioned fear and anxiety-like behaviors

Cited by 81 publications

References 78 publications

Neurocognitive and Biomarker Evaluation of Combination mTBI from Blast Overpressure and Traumatic Stress

Neurocognitive and Biomarker Evaluation of Combination mTBI from Blast Overpressure and Traumatic Stress

Early and Persistent Dendritic Hypertrophy in the Basolateral Amygdala following Experimental Diffuse Traumatic Brain Injury

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

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