Posttraumatic stress disorder in patients with traumatic brain injury and amnesia for the event?

Warden, Deborah L.; Labbate, Lawrence A.; Salazar, Andrés M.; Nelson, Rebekah J.; Sheley, Erin L.; Staudenmeier, James J.; Martin, Erica

doi:10.1176/jnp.9.1.18

Cited by 78 publications

(6 citation statements)

References 14 publications

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“…This implies that the enhanced processing in the amygdala in response to a traumatic cue is not significantly influenced by the mTBI or loss of consciousness in our model and, as such, mTBI does not fully guarantee protection from trauma-related intrusive memories or PTSD symptoms. Our data demonstrating the differential effect of mTBI on both Contextual and discrete Cued fear memory responses are in agreement with the human study literature showing inconclusive and sometimes conflicting results on the prevalence of PTSD in some mTBI cases; in particular, this agrees with the observation that some of these patients only elicit partial (and fewer) intrusive clusters of PTSD symptoms that do not fully meet the criteria for the disorder (Ohry et al, 1996; Warden et al, 1997; Gil et al, 2005; Bryant, 2008). Three other animal models involving a single lateral fluid percussion injury, repetitive (×2) closed head injury and repetitive (×3) blast over-pressure injury have investigated the influence of mTBI on fear conditioning (Witgen et al, 2005; Elder et al, 2012; Klemenhagen et al, 2013).…”

Section: Discussionsupporting

confidence: 92%

Neurobehavioral, neuropathological and biochemical profiles in a novel mouse model of co-morbid post-traumatic stress disorder and mild traumatic brain injury

Ojo

Greenberg

Leary

et al. 2014

Front. Behav. Neurosci.

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Co-morbid mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) has become the signature disorder for returning combat veterans. The clinical heterogeneity and overlapping symptomatology of mTBI and PTSD underscore the need to develop a preclinical model that will enable the characterization of unique and overlapping features and allow discrimination between both disorders. This study details the development and implementation of a novel experimental paradigm for PTSD and combined PTSD-mTBI. The PTSD paradigm involved exposure to a danger-related predator odor under repeated restraint over a 21 day period and a physical trauma (inescapable footshock). We administered this paradigm alone, or in combination with a previously established mTBI model. We report outcomes of behavioral, pathological and biochemical profiles at an acute timepoint. PTSD animals demonstrated recall of traumatic memories, anxiety and an impaired social behavior. In both mTBI and combination groups there was a pattern of disinhibitory like behavior. mTBI abrogated both contextual fear and impairments in social behavior seen in PTSD animals. No major impairment in spatial memory was observed in any group. Examination of neuroendocrine and neuroimmune responses in plasma revealed a trend toward increase in corticosterone in PTSD and combination groups, and an apparent increase in Th1 and Th17 proinflammatory cytokine(s) in the PTSD only and mTBI only groups respectively. In the brain there were no gross neuropathological changes in any groups. We observed that mTBI on a background of repeated trauma exposure resulted in an augmentation of axonal injury and inflammatory markers, neurofilament L and ICAM-1 respectively. Our observations thus far suggest that this novel stress-trauma-related paradigm may be a useful model for investigating further the overlapping and distinct spatio-temporal and behavioral/biochemical relationship between mTBI and PTSD experienced by combat veterans.

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Section: Discussionsupporting

confidence: 92%

Neurobehavioral, neuropathological and biochemical profiles in a novel mouse model of co-morbid post-traumatic stress disorder and mild traumatic brain injury

Ojo

Greenberg

Leary

et al. 2014

Front. Behav. Neurosci.

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“…For more chronic symptoms, the standing recommendation for treatment of post-concussion conditions is a symptoms-based approach [ 1 ]. Although the current treatment methods promote patient recovery from some mTBI symptoms, this approach may fail to address the underlying etiology and pathophysiology of concussions resulting in longitudinal alterations in cognitive, occupational, emotional, and neuromuscular function [ 4 - 7 ]. Consequently, a standard for care that addresses and treats the underlying pathology is needed for effective treatment of post-concussion symptoms.…”

Section: Introductionmentioning

confidence: 99%

Developing the Standard of Care for Post-Concussion Treatment: Neuroimaging-Guided Rehabilitation of Neurovascular Coupling

Wing¹,

Tucker²,

Fong³

et al. 2017

TONIJ

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Background:Emerging research proposes the imbalance between microvascular supply and metabolic demand as a contributing factor in the pathophysiology of mild traumatic brain injury. Prolonged effects on the dysregulation of neurovascular coupling may explain persistent symptomatic models such as Post-Concussion Syndrome.Objective:Increased knowledge of what we refer to as neurovascular uncoupling provides a template for establishing a new concussion treatment standard in the assessment and therapeutic guidance of concussion.Methods:The degree and localization of neurovascular uncoupling were statistically contextualized against a normative-based atlas in 270 concussed patients. Functional NeuroCognitive ImagingTM was used to establish pre-treatment benchmarks and guide neurotherapy. Conventional and functional neurocognitive imaging-directed measures were used to evaluate post-rehabilitative outcomes.Results:Functional neurocognitive imaging was successful in identifying regions of Neurovascular uncoupling unique to each patient’s brain and concussion profile. Longitudinal objective outcome measures demonstrated timely and lasting improvement of neurovascular coupling functioning in a significant majority of patients.Conclusion:We present practice-based evidence supporting the clinical administration of functional neurocognitive imaging with particular efficacy in the neurorehabilitation of concussion. We advocate the reliability of functional neurocognitive imaging in assessing severity and localization of neurovascular uncoupling, and promote its use in the therapeutic guidance and neurorehabilitation of mild traumatic brain injury. We further support the continual exploration of other potential pathophysiological alterations resulting from concussion.

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“…These symptoms indicate damage to the hippocampus (HC) and the prefrontal cortex (PFC), brain structures that are also indicated as the neuroanatomical substrates of PTSD (Jaffee and Meyer, 2009). Stress is a constant factor on the battlefield (Warden et al, 1997; Brenner et al, 2009); soldiers are repeatedly exposed to various life-threatening situations and to the visual and audible cues of blasts without necessarily suffering from any visible physical injury.…”

Section: Introductionmentioning

confidence: 99%

Stress and Traumatic Brain Injury: A Behavioral, Proteomics, and Histological Study

Kwon¹,

Kövesdi²,

György³

et al. 2011

Front. Neur.

112

119

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Psychological stress and traumatic brain injury (TBI) can both result in lasting neurobehavioral abnormalities. Post-traumatic stress disorder and blast induced TBI (bTBI) have become the most significant health issues in current military conflicts. Importantly, military bTBI virtually never occurs without stress. In this experiment, we assessed anxiety and spatial memory of rats at different time points after repeated exposure to stress alone or in combination with a single mild blast. At 2 months after injury or sham we analyzed the serum, prefrontal cortex (PFC), and hippocampus (HC) of all animals by proteomics and immunohistochemistry. Stressed sham animals showed an early increase in anxiety but no memory impairment at any measured time point. They had elevated levels of serum corticosterone (CORT) and hippocampal IL-6 but no other cellular or protein changes. Stressed injured animals had increased anxiety that returned to normal at 2 months and significant spatial memory impairment that lasted up to 2 months. They had elevated serum levels of CORT, CK-BB, NF-H, NSE, GFAP, and VEGF. Moreover, all of the measured protein markers were elevated in the HC and the PFC; rats had an increased number of TUNEL-positive cells in the HC and elevated GFAP and Iba1 immunoreactivity in the HC and the PFC. Our findings suggest that exposure to repeated stress alone causes a transient increase in anxiety and no significant memory impairment or cellular and molecular changes. In contrast, repeated stress and blast results in lasting behavioral, molecular, and cellular abnormalities characterized by memory impairment, neuronal and glial cell loss, inflammation, and gliosis. These findings may have implications in the development of diagnostic and therapeutic measures for conditions caused by stress or a combination of stress and bTBI.

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Posttraumatic stress disorder in patients with traumatic brain injury and amnesia for the event?

Cited by 78 publications

References 14 publications

Neurobehavioral, neuropathological and biochemical profiles in a novel mouse model of co-morbid post-traumatic stress disorder and mild traumatic brain injury

Neurobehavioral, neuropathological and biochemical profiles in a novel mouse model of co-morbid post-traumatic stress disorder and mild traumatic brain injury

Developing the Standard of Care for Post-Concussion Treatment: Neuroimaging-Guided Rehabilitation of Neurovascular Coupling

Stress and Traumatic Brain Injury: A Behavioral, Proteomics, and Histological Study

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