Behavioral responses following repeated bilateral frontal region closed head impacts and fear conditioning in male and female mice

Vu, Patricia A.; McNamara, Eileen H.; Liu, Jiong; Tucker, Laura B.; Fu, Amanda H.; McCabe, Joseph T.

doi:10.1016/j.brainres.2020.147147

Cited by 5 publications

(5 citation statements)

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“…Poorer performance on visible platform trials following multiple CHIMERA injuries has been reported in another recent study, which also found impaired performance on a visual cliff task and reduced visual evoked potentials, providing further evidence for behavioral and physiological visual dysfunction. 38 Like many other murine models of CBI, with or without rotational acceleration, 13 , 39–42 , 46 , 70-72 pathological analysis of mice following CHIMERA (including the current study) finds significant and often prolonged increased astrogliosis and/or microgliosis in the optic tracts as assessed by GFAP or Iba1 staining, respectively. 14 , 38 , 66 Decreased performance on the optokinetic behavioral response test, coupled with decreases in the number of retinal ganglion cells, has also been reported following single or repeated concussive TBI.…”

Section: Discussionsupporting

confidence: 52%

“…The context test in the DFC paradigm is hippocampal-dependent, and contextual FC is often utilized as a specific behavioral test of hippocampal function. 75-77 Deficits on the DFC context test in male mice have been reported following fluid percussion injury, 76–80 repetitive CBI, 39 , 70 , 75 and blast neurotrauma. 74 …”

Section: Discussionmentioning

confidence: 99%

“…The context test in the DFC paradigm is hippocampaldependent, and contextual FC is often utilized as a specific behavioral test of hippocampal function. [75][76][77] Deficits on the DFC context test in male mice have been reported following fluid percussion injury, [76][77][78][79][80] repetitive CBI, 39,70,75 and blast neurotrauma. 74 Neural underpinnings of cognitive dysfunction following CHIMERA No pathology was found here to account for the behavioral deficits observed.…”

Section: Summary Of Pathological Findingsmentioning

confidence: 99%

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Hippocampal-Dependent Cognitive Dysfunction following Repeated Diffuse Rotational Brain Injury in Male and Female Mice

Tucker

McCabe

2021

Journal of Neurotrauma

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Cognitive dysfunction is a common, often long-term complaint following acquired traumatic brain injury (TBI). Cognitive deficits suggest dysfunction in hippocampal circuits. The goal of the studies described here is to phenotype in both male and female mice the hippocampal-dependent learning and memory deficits resulting from TBI sustained by the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) device-a model that delivers both a contact-concussion injury as well as unrestrained rotational head movement. Mice sustained either sham procedures or four injuries (0.7 J, 24-h intervals). Spatial learning and memory skills assessed in the Morris water maze (MWM) approximately 3 weeks following injuries were significantly impaired by brain injuries; however, slower swimming speeds and poor performance on visible platform trials suggest that measurement of cognitive impairment with this test is confounded by injury-induced motor and/or visual impairments. A separate experiment confirmed hippocampal-dependent cognitive deficits with trace fear conditioning (TFC), a behavioral test less dependent on motor and visual function. Male mice had greater injury-induced deficits on both the MWM and TFC tests than female mice. Pathologically, the injury was characterized by white matter damage as observed by silver staining and glial fibrillary acidic protein (astrogliosis) in the optic tracts, with milder damage seen in the corpus callosum, and fimbria and brainstem (cerebral peduncles) of some animals. No changes in the density of GABAergic parvalbumin-expressing cells in the hippocampus, amygdala, or parietal cortex were found. This experiment confirmed significant sexually dimorphic cognitive impairments following a repeated, diffuse brain injury.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Summary Of Pathological Findingsmentioning

confidence: 99%

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Hippocampal-Dependent Cognitive Dysfunction following Repeated Diffuse Rotational Brain Injury in Male and Female Mice

Tucker

McCabe

2021

Journal of Neurotrauma

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“…This "impulsive" behavior has been described as increased time and entries to the open arms or quadrants of the EPM or EZM in injured rodents, and this could be related to changes in overall arousal due to TBI (Mannix et al, 2014;Mouzon et al, 2014;Gold et al, 2018;Tucker et al, 2019). Hyperactivity has been reported in multiple experimental models of TBI, including CCI (Kimbler et al, 2012;Budinich et al, 2013;Hsieh et al, 2014;Bajwa et al, 2016; and repetitive concussive brain injury (Kane et al, 2012;Mannix et al, 2014;Tucker et al, 2019;Vu et al, 2020). Dissociating anxiety from activity and impulsivity has long been a point of discussion in translational anxiety research (Dawson and Tricklebank, 1995;Weiss et al, 1998;Cryan and Holmes, 2005).…”

Section: Consideration Of Potential Testing Confoundsmentioning

confidence: 99%

Measuring Anxiety-Like Behaviors in Rodent Models of Traumatic Brain Injury

Tucker

McCabe

2021

Front. Behav. Neurosci.

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Anxiety is a common complaint following acquired traumatic brain injury (TBI). However, the measurement of dysfunctional anxiety behavioral states following experimental TBI in rodents is complex. Some studies report increased anxiety after TBI, whereas others find a decreased anxiety-like state, often described as increased risk-taking behavior or impulsivity. These inconsistencies may reflect a lack of standardization of experimental injury models or of behavioral testing techniques. Here, we review the most commonly employed unconditioned tests of anxiety and discuss them in a context of experimental TBI. Special attention is given to the effects of repeated testing, and consideration of potential sensory and motor confounds in injured rodents. The use of multiple tests and alternative data analysis methods are discussed, as well as the potential for the application of common data elements (CDEs) as a means of providing a format for documentation of experimental details and procedures of each published research report. CDEs may improve the rigor, reproducibility, as well as endpoint for better relating findings with clinical TBI phenotypes and the final goal of translation. While this may not resolve all incongruities in findings across laboratories, it is seen as a way forward for standardized and universal data collection for improvement of data quality and sharing, and advance therapies for neuropsychiatric symptoms that often present for decades following TBI.

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“…Hyperactivity has been observed in females during open field tests following controlled cortical impact ( Tucker et al, 2016 , 2017 ). Likewise, a recent study with repetitive concussive injuries directed at the frontal region likewise observed increased distance travelled in the open field test, and that female mice travelled farther in an acute test 4 days after injury, but not at later time points ( Vu et al, 2021 ). The higher levels of activity, particularly in females as observed in the EPM and in open field in other studies, could be related to activational effects of estrogen ( Morgan and Pfaff, 2002 ; Ogawa et al, 2003 ), but further investigation is needed to understand the mechanism and duration of this increased activity in female mice after blast.…”

Section: Discussionmentioning

confidence: 79%

Limbic Responses Following Shock Wave Exposure in Male and Female Mice

McNamara

Tucker²,

Liu³

et al. 2022

Front. Behav. Neurosci.

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Blast traumatic brain injury (bTBI) presents a serious threat to military personnel and often results in psychiatric conditions related to limbic system dysfunction. In this study, the functional outcomes for anxiety- and depressive-like behaviors and neuronal activation were evaluated in male and female mice after exposure to an Advanced Blast Simulator (ABS) shock wave. Mice were placed in a ventrally exposed orientation inside of the ABS test section and received primary and tertiary shock wave insults of approximately 15 psi peak pressure. Evans blue staining indicated cases of blood-brain barrier breach in the superficial cerebral cortex four, but not 24 h after blast, but the severity was variable. Behavioral testing with the elevated plus maze (EPM) or elevated zero maze (EZM), sucrose preference test (SPT), and tail suspension test (TST) or forced swim test (FST) were conducted 8 days–3.5 weeks after shock wave exposure. There was a sex difference, but no injury effect, for distance travelled in the EZM where female mice travelled significantly farther than males. The SPT and FST did not indicate group differences; however, injured mice were less immobile than sham mice during the TST; possibly indicating more agitated behavior. In a separate cohort of animals, the expression of the immediate early gene, c-Fos, was detected 4 h after undergoing bTBI or sham procedures. No differences in c-Fos expression were found in the cerebral cortex, but female mice in general displayed enhanced c-Fos activation in the paraventricular nucleus of the thalamus (PVT) compared to male mice. In the amygdala, more c-Fos-positive cells were observed in injured animals compared to sham mice. The observed sex differences in the PVT and c-Fos activation in the amygdala may correlate with the reported hyperactivity of females post-injury. This study demonstrates, albeit with mild effects, behavioral and neuronal activation correlates in female rodents after blast injury that could be relevant to the incidence of increased post-traumatic stress disorder in women.

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Behavioral responses following repeated bilateral frontal region closed head impacts and fear conditioning in male and female mice

Cited by 5 publications

References 82 publications

Hippocampal-Dependent Cognitive Dysfunction following Repeated Diffuse Rotational Brain Injury in Male and Female Mice

Hippocampal-Dependent Cognitive Dysfunction following Repeated Diffuse Rotational Brain Injury in Male and Female Mice

Measuring Anxiety-Like Behaviors in Rodent Models of Traumatic Brain Injury

Limbic Responses Following Shock Wave Exposure in Male and Female Mice

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