A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

Mychasiuk, Richelle; Farran, Allyson; Angoa‐Pérez, Mariana; Briggs, Denise I.; Kuhn, Donald M.; Esser, Michael J.

doi:10.3791/51820

Cited by 62 publications

(60 citation statements)

References 7 publications

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“…Velocity of the impacting device at time of impact ranged from 3.13 m/s (Mychasiuk, Farran, Angoa‐Perez, et al, ; Mychasiuk, Farran, & Esser, ; Mychasiuk, Hehar, Candy, Ma, & Esser, ; Mychasiuk, Hehar, & Esser, ; Mychasiuk, Hehar, Farran, & Esser, ; Mychasiuk, Hehar, Ma, & Esser, ; Mychasiuk, Hehar, Ma, Kolb, & Esser, ; Mychasiuk, Hehar, van Waes, & Esser, ) to 11.2 m/s (Bolouri, Saljo, Viano, & Hamberger, ; Hamberger et al, ; Viano et al, ). Weights contacting the head ranged from 50g (Bolouri et al, ; Hamberger et al, ; Viano et al, ) to 450g (Viano et al, ).…”

Section: Resultsmentioning

confidence: 99%

Modeling sports‐related mild traumatic brain injury in animals—A systematic review

Hiskens

Angoa‐Pérez

Schneiders

et al. 2019

J of Neuroscience Research

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Sports-related head trauma has emerged as an important public health issue, as mild traumatic brain injuries (mTBIs) may result in neurodegenerative disorders such as chronic traumatic encephalopathy (CTE). Research into mTBI and CTE pathophysiology are difficult to undertake in athletes, with observational trials and post-mortem analysis the current mainstays. Thus, animal models play an important role in the study of mTBI, however, traditional animal models have focused on acute, severe injuries rather than the more typical mTBI's seen in sport injuries. Recently, a number of animal models have been developed that are both appropriately scaled and biomechanically relevant to the forces sustained by athletes. This review aimed to examine the literature for variables included in these animal models, and the resulting neurotrauma as evidenced by pathology and behavioral deficits. A systematic search of the literature was performed in multiple electronic databases. The inclusion criteria required mimicry of athlete mTBI conditions: freedom of head movement, lack of surgical alteration of the skull, and application of direct contact force. Studies were analyzed for variables including apparatus design features (impact force, change in animal head velocity, and kinetic energy transfer to the head), demonstrated pathology (phosphorylated tau, TDP-43 aggregation, diffuse axonal injury, gliosis, cytokine inflammation response, and genetic integrity), and behavioral changes. These studies suggested that appropriate animal models can assist in understanding the pathological and functional outcomes of athlete mTBI, and could be used as a platform for future studies of diagnostic/prognostic markers and in the development of treatment interventions. K E Y W O R D S animal models, chronic traumatic encephalopathy, concussion, neurotrauma | INTRODUC TI ONAthlete head impacts continue to attract significant media and research attention with sports such as soccer, football, ice hockey, lacrosse, and rugby displaying significant rates of head injury in American high school and collegiate athletes O'Connor et al., 2017). These impacts occur across a continuum of severity; from injuries resulting in unconsciousness and requiring the athlete to be assisted on the field, to contact with no immediate observable consequences, such as heading a soccer ball. The nature of many of these sports predicates that head impacts are not sustained in isolation, but are often an intrinsic by-product of the rules of the sport, and as such are repetitively sustained across a match | 1195 HISKENS Et al.

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Section: Resultsmentioning

confidence: 99%

Modeling sports‐related mild traumatic brain injury in animals—A systematic review

Hiskens

Angoa‐Pérez

Schneiders

et al. 2019

J of Neuroscience Research

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“…The behavioral test battery spanned 14 days (P54‐68) and consisted of the beam walking task (P54), open field (P55), elevated plus maze (EPM; P56), novel context mismatch (NCM; P59‐62), von Frey (P66), and forced swim (P68). These behavioral tests have been outlined in detail by our laboratory group previously (Mychasiuk, Farran, et al, ; Mychasiuk et al, ; Salberg, ). In brief, the beam walking task involved the measurement of hind leg foot slips that occurred as the animals traversed a tapered beam, providing an assessment of balance and motor coordination (Schallert et al,).…”

Section: Methodsmentioning

confidence: 99%

Caffeine consumption during development alters spine density and recovery from repetitive mild traumatic brain injury in young adult rats

Christensen

Yamakawa

Salberg

et al. 2019

Synapse

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Caffeine is the most commonly used psychostimulant throughout the world, with its consumption being especially prevalent among adolescents and young adults, as over 75% of this group consumes caffeine daily. Similarly, the adolescent and young adult age group exhibit the highest incidence of traumatic brain injury (TBI). Given that both caffeine consumption and mild TBI (mTBI) are more prevalent among the late adolescent/young adult age group and that changes in dendritic spine morphology during this developmental period are poorly understood, this study sought to examine the effects of caffeine consumption during late adolescence/early adulthood on recovery from repetitive mTBI (RmTBI). The study specifically focused on changes to neuronal dendritic morphology as synaptic changes likely underlie long-term behavioral outcomes. The results demonstrate that during young adulthood caffeine consumption differentially affects the RmTBI outcomes of males and females, where the effects of caffeine and RmTBI were often additive in males while being equally detrimental, but rarely additive, in females. In general, caffeine and RmTBI induced the greatest impairments in males on cognitive and motor tasks whereas in females the most significant detriments were on pain-related tasks. Both caffeine and RmTBI increased spine density in the Cg3 (medial prefrontal cortex [mPFC]), AID (orbitofrontal cortex [OFC]), and nucleus accumbens (NAc), which is proposed to reflect an impairment in the normal pruning processes. Overall, despite caffeine's neuroprotective abilities among other age groups, this study offers concerning results regarding the detrimental effects of caffeine and RmTBI, in isolation, and especially in combination, in this susceptible population. K E Y W O R D Sadolescent, behavior, concussion, dendritic morphology, Golgi-Cox staining, nucleus accumbens, prefrontal cortex

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“…Beam walking is a balance and motor coordination procedure used to measure foot‐slips on a tapered beam, similar to that described by Schallert et al . () and described in detail in our previous studies (Mychasiuk et al ., ,b). The test was carried out PID1 and PID 11.…”

Section: Methodsmentioning

confidence: 99%

Reducing the time interval between concussion and voluntary exercise restores motor impairment, short‐term memory, and alterations to gene expression

Mychasiuk

Hehar

et al. 2016

Eur J of Neuroscience

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Despite the most common form of brain injury, there has been little progress in the prognosis and treatment of concussion/mild traumatic brain injury (mTBI). Current 'return-to-play' guidelines are conservative, deterring the initiation of physical and social activity until patients are asymptomatic; but the effects of post-injury exercise have not been adequately investigated. Therefore, this study examined the effects of voluntary exercise on concussion recovery. Using a translational rodent model of concussion, we examined the influence of exercise on injury-associated behaviours that comprise post-concussive syndrome (PCS) and gene expression changes (bdnf, dnmt1, Igf-1, pgc1-a, Tert) in prefrontal cortex and hippocampus. In addition, as we have previously demonstrated telomere length (TL) to be a reliable predictor of mTBI prognosis, TL was also examined. The results suggest that exercise initiated within 1-3 days post-concussion significantly improved motor and cognitive functioning, but had limited efficacy treating emotional impairments. What is more, when deprived of social interaction and exercise, a combination similar to clinical recommendations for rest until symptom resolution, animals did not recover and exhibited impairments similar to typical mTBI animals. Exercise aided in restoration of mTBI-induced modifications to gene expression in both brain regions. An inverse relationship between the exercise return interval and TL was identified, indicating greater recovery with acute exercise reinstatement. Although additional strategies may need to be employed for emotional functioning, these findings support re-evaluation of 'returnto-play' guidelines, suggesting that exercise is valuable for the treatment of concussion.

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A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

Cited by 62 publications

References 7 publications

Modeling sports‐related mild traumatic brain injury in animals—A systematic review

Modeling sports‐related mild traumatic brain injury in animals—A systematic review

Caffeine consumption during development alters spine density and recovery from repetitive mild traumatic brain injury in young adult rats

Reducing the time interval between concussion and voluntary exercise restores motor impairment, short‐term memory, and alterations to gene expression

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