Mean girls: Sex differences in the effects of mild traumatic brain injury on the social dynamics of juvenile rat play behaviour

Mychasiuk, Richelle; Hehar, Harleen; Farran, Allyson; Esser, Michael J.

doi:10.1016/j.bbr.2013.10.048

Cited by 55 publications

(52 citation statements)

References 40 publications

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“…Previous studies in our laboratories have also found evidence for sex‐dependent outcomes in rodent models of TBI 65, 66. For example, there are sex‐dependent social deficits in juvenile mice given a mild TBI 66. Another study found that juvenile males and females did not differ on a range of sensorimotor outcomes, which is consistent with our findings of motor‐related deficits in both male and female rats given RmTBI 67.…”

Section: Discussionsupporting

confidence: 91%

“…Males given mTBIs exhibited greater impairment on the cognitive task (i.e., NCM), whereas females given mTBIs exhibited increased impairments on the forced swim task. Previous studies in our laboratories have also found evidence for sex‐dependent outcomes in rodent models of TBI 65, 66. For example, there are sex‐dependent social deficits in juvenile mice given a mild TBI 66.…”

Section: Discussionmentioning

confidence: 58%

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Sex matters: repetitive mild traumatic brain injury in adolescent rats

Wright

O’Brien

Shultz

et al. 2017

Ann Clin Transl Neurol

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ObjectiveWhether sex differences contribute to the heterogeneity of mild traumatic brain injury (mTBI) and repeated mTBI (RmTBI) outcomes in adolescents is unknown. Therefore, this study examined changes in, and differences between, male and female rats following single mTBI and RmTBI.MethodsRats were given a single mTBI, RmTBI (i.e., 3x), or sham injuries. Injuries were administered using a lateral impact model that mimics forces common in human mTBI. After the final injury, rats underwent extensive behavioral testing to examine cognition, motor function, and anxiety‐ and depressive‐like behavior. Postmortem analyses investigated gene expression and structural changes in the brain.ResultsMany of the outcomes exhibited a sex‐dependent response to RmTBI. While all rats given RmTBI had deficits in balance, motor coordination, locomotion, and anxiety‐like behavior, only male rats given RmTBI had short‐term working memory deficits, whereas only females given RmTBI had increased depressive‐like behavior. Volumetric and diffusion weighted MRI analyses found that while RmTBI‐induced atrophy of the prefrontal cortex was greater in female rats, only the male rats exhibited worse white matter integrity in the corpus callosum following RmTBI. Sex‐dependent changes in brain expression of mRNA for glial fibrillary acidic protein, myelin basic protein, and tau protein were also observed following injury.InterpretationThese findings suggest that in adolescent mTBI, sex matters; and future studies incorporating both male and females are warranted to provide a greater understanding of injury prognosis and better inform clinical practice.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 58%

Sex matters: repetitive mild traumatic brain injury in adolescent rats

Wright

O’Brien

Shultz

et al. 2017

Ann Clin Transl Neurol

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“…Additionally, the model produces clinically relevant symptomology. Juvenile rodents that experienced a single mTBI demonstrated deficits in balance and motor behaviours, along with deficits in executive function, increased depressive-like behaviours, and altered social interactions 6,9 . Similarly, adult mice also display mild balance and coordination deficits that recover with time 7 .…”

Section: Representative Resultsmentioning

confidence: 99%

A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

Mychasiuk

Farran

Angoa‐Pérez

et al. 2014

JoVE

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Despite growing evidence that childhood represents a major risk period for mild traumatic brain injury (mTBI) from sports-related concussions, motor vehicle accidents, and falls, a reliable animal model of mTBI had previously not been developed for this important aspect of development. The modified weight-drop technique employs a glancing impact to the head of a freely moving rodent transmitting acceleration, deceleration, and rotational forces upon the brain. When applied to juvenile rats, this modified weight-drop technique induced clinically relevant behavioural outcomes that were representative of post-concussion symptomology. The technique is a rapidly applied procedure with an extremely low mortality rate, rendering it ideal for high-throughput studies of therapeutics. In addition, because the procedure involves a mild injury to a closed head, it can easily be used for studies of repetitive brain injury. Owing to the simplistic nature of this technique, and the clinically relevant biomechanics of the injury pathophysiology, the modified weight-drop technique provides researchers with a reliable model of mTBI that can be used in a wide variety of behavioural, molecular, and genetic studies.

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“…A second juvenile model has been developed by adapting the Wayne State method, whereby p28-30 rats undergo horizontal rotation upon impact [62,66,67]. Using this model, a single mTBI results in changes in cognitive and psychosocial behavior [38,67], and a succession of 10 daily impacts impaired vestibulomotor function acutely, which was resolved by 1 month postimpact [62]. Together, these existing models, while limited in scope in terms of evaluation of acute and chronic neuropathology and longer-term outcomes, represent an important first step in understanding how the adolescent brain responds to mTBI.…”

Section: Discussionmentioning

confidence: 99%

“…In mice that received isoflurane anesthesia during surgical procedures, righting reflex was evaluated as the latency to return upright from a supine position [38]. …”

Section: Methodsmentioning

confidence: 99%

Long-Term Anesthetic-Dependent Hypoactivity after Repetitive Mild Traumatic Brain Injuries in Adolescent Mice

et al. 2016

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Recent evidence supports the hypothesis that repetitive mild traumatic brain injuries (rmTBIs) culminate in neurological impairments and chronic neurodegeneration, which have wide-ranging implications for patient management and return-to-play decisions for athletes. Adolescents show a high prevalence of sports-related head injuries and may be particularly vulnerable to rmTBIs due to ongoing brain maturation. However, it remains unclear whether rmTBIs, below the threshold for acute neuronal injury or symptomology, influence long-term outcomes. To address this issue, we first defined a very mild injury in adolescent mice (postnatal day 35) as evidenced by an increase in Iba-1- labeled microglia in white matter in the acutely injured brain, in the absence of indices of cell death, axonal injury, and vasogenic edema. Using this level of injury severity and Avertin (2,2,2-tribromoethanol) as the anesthetic, we compared mice subjected to either a single mTBI or 2 rmTBIs, each separated by 48 h. Neurobehavioral assessments were conducted at 1 week and at 1 and 3 months postimpact. Mice subjected to rmTBIs showed transient anxiety and persistent and pronounced hypoactivity compared to sham control mice, alongside normal sensorimotor, cognitive, social, and emotional function. As isoflurane is more commonly used than Avertin in animal models of TBI, we next examined long-term outcomes after rmTBIs in mice that were anesthetized with this agent. However, there was no evidence of abnormal behaviors even with the addition of a third rmTBI. To determine whether isoflurane may be neuroprotective, we compared the acute pathology after a single mTBI in mice anesthetized with either Avertin or isoflurane. Pathological findings were more pronounced in the group exposed to Avertin compared to the isoflurane group. These collective findings reveal distinct behavioral phenotypes (transient anxiety and prolonged hypoactivity) that emerge in response to rmTBIs. Our findings further suggest that selected anesthetics may confer early neuroprotection after rmTBIs, and as such mask long-term abnormal phenotypes that may otherwise emerge as a consequence of acute pathogenesis.

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Mean girls: Sex differences in the effects of mild traumatic brain injury on the social dynamics of juvenile rat play behaviour

Cited by 55 publications

References 40 publications

Sex matters: repetitive mild traumatic brain injury in adolescent rats

Sex matters: repetitive mild traumatic brain injury in adolescent rats

A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

Long-Term Anesthetic-Dependent Hypoactivity after Repetitive Mild Traumatic Brain Injuries in Adolescent Mice

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