Environmental enrichment protects against functional deficits caused by traumatic brain injury

Johnson, Erica M.; Traver, Kyle; Hoffman, Stuart W.; Harrison, Catherine; Herman, James P.

doi:10.3389/fnbeh.2013.00044

Cited by 55 publications

(51 citation statements)

References 51 publications

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“…However, high variability is a limitation common to most in vivo studies, particularly in the area of animal behavior. The coefficients of variation for similar EPM metrics from other concussion studies were consistent with the current findings (35 to 68% for open area duration),22,33 and in some cases exceeded 100% 1. Therefore, somewhat weak correlations were expected due to the inherent variability of rodent behavioral data.…”

Section: Discussionsupporting

confidence: 90%

Prediction of Post-Concussive Behavioral Changes in a Rodent Model Based on Head Rotational Acceleration Characteristics

et al. 2016

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Quantifying injury tolerance for concussion is complicated by variability in the type, severity, and time course of post-injury physiological and behavioral changes. The current study outlined acute and chronic changes in behavioral metrics following rotational acceleration-induced concussion in rats. The Medical College of Wisconsin (MCW) rotational injury model independently controlled magnitude and duration of the rotational acceleration pulse. Increasing rotational acceleration magnitude produced longer recovery times, which were used in this study and our prior work as an assessment of acute injury severity. However, longer duration rotational accelerations produced changes in emotionality as measured using the elevated plus maze. Cognitive deficits were for the most part not apparent in the Morris water maze assessment, possibly due to the lower severity of rotational acceleration pulses incorporated in this study. Changes in emotionality evolved between acute and chronic assessments, in some cases increasing in severity and in others reversing polarity. These findings highlight the complexity of quantifying injury tolerance for concussion and demonstrate a need to incorporate rotational acceleration magnitude and duration in proposed injury tolerance metrics. Rotational velocity on its own was not a strong predictor of the magnitude or type of acute behavioral changes following concussion, although its combination with rotational acceleration magnitude using multivariate analysis was the strongest predictor for acute recovery time and some chronic emotional-type behavioral changes.

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Section: Discussionsupporting

confidence: 90%

Prediction of Post-Concussive Behavioral Changes in a Rodent Model Based on Head Rotational Acceleration Characteristics

et al. 2016

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“…Impulsive-like behavior becomes evident in rodents with damage to the lateral orbitofrontal cortex (Mar et al, 2011; Bidzan et al, 2012; Johnson et al, 2013). …”

Section: Resultsmentioning

confidence: 99%

Salubrinal reduces oxidative stress, neuroinflammation and impulsive-like behavior in a rodent model of traumatic brain injury

et al. 2016

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Traumatic brain injury (TBI) is the leading cause of trauma related morbidity in the developed world. TBI has been shown to trigger secondary injury cascades including endoplasmic reticulum (ER) stress, oxidative stress, and neuroinflammation. The link between secondary injury cascades and behavioral outcome following TBI is poorly understood warranting further investigation. Using our validated rodent blast TBI model, we examined the interaction of secondary injury cascades following single injury and how these interactions may contribute to impulsive-like behavior after a clinically relevant repetitive TBI paradigm. We targeted these secondary pathways acutely following single injury with the cellular stress modulator, salubrinal (SAL). We examined the neuroprotective effects of SAL administration on significantly reducing ER stress: janus-N-terminal kinase (JNK) phosphorylation and C/EBP homology protein (CHOP), oxidative stress: superoxide and carbonyls, and neuroinflammation: nuclear factor kappa beta (NFκB) activity, inducible nitric oxide synthase (iNOS) protein expression, and pro-inflammatory cytokines at 24 h post-TBI. We then used the more clinically relevant repeat injury paradigm and observed elevated NFκB and iNOS activity. These injury cascades were associated with impulsive-like behavior measured on the elevated plus maze. SAL administration attenuated secondary iNOS activity at 72 h following repetitive TBI, and most importantly prevented impulsive-like behavior. Overall, these results suggest a link between secondary injury cascades and impulsive-like behavior that can be modulated by SAL administration.

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“…Enrichment was initiated 1 week prior to chronic stress to allow habituation to the enriched environment and avoid any compounding effects of initiating the two manipulations simultaneously (see Johnson, Traver, Hoffman, Harrison, & Herman, 2013 for photograph of the enrichment chambers). Rats were exposed to active cycle environmental enrichment as previously published (Smith et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

Adolescent environmental enrichment prevents behavioral and physiological sequelae of adolescent chronic stress in female (but not male) rats

Smith

Morano

Ulrich‐Lai

et al. 2017

Stress

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The late adolescent period is characterized by marked neurodevelopmental and endocrine fluctuations in the transition to early adulthood. Adolescents are highly responsive to the external environment, which enhances their ability to adapt and recover from challenges when given nurturing influences, but also makes them vulnerable to aberrant development when exposed to prolonged adverse situations. Female rats are particularly sensitive to the effects of chronic stress in adolescence, which manifests as passive coping strategies and blunted hypothalamo-pituitary adrenocortical (HPA) stress responses in adulthood. We sought to intervene by exposing adolescent rats to environmental enrichment (EE) immediately prior to and during chronic stress, hypothesizing that EE would minimize or prevent the long-term effects of stress that emerge in adult females. To test this, we exposed male and female rats to EE on postnatal days (PND) 33–60 and implemented chronic variable stress (CVS) on PND 40–60. CVS consisted of twice-daily unpredictable stressors. Experimental groups included: CVS/unenriched, unstressed/EE, CVS/EE and unstressed/unenriched (n = 10 of each sex/group). In adulthood, we measured behavior in the open field test and forced swim test (FST) and collected blood samples following the FST. We found that environmental enrichment given during the adolescent period prevented the chronic stress-induced transition to passive coping in the FST and reversed decreases in peak adrenocortical responsiveness observed in adult females. Adolescent enrichment had little to no effect on males or unstressed females tested in adulthood, indicating that beneficial effects are specific to females that were exposed to chronic stress.

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Environmental enrichment protects against functional deficits caused by traumatic brain injury

Cited by 55 publications

References 51 publications

Prediction of Post-Concussive Behavioral Changes in a Rodent Model Based on Head Rotational Acceleration Characteristics

Prediction of Post-Concussive Behavioral Changes in a Rodent Model Based on Head Rotational Acceleration Characteristics

Salubrinal reduces oxidative stress, neuroinflammation and impulsive-like behavior in a rodent model of traumatic brain injury

Adolescent environmental enrichment prevents behavioral and physiological sequelae of adolescent chronic stress in female (but not male) rats

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