Traumatic brain injury in adolescence: A review of the neurobiological and behavioural underpinnings and outcomes

Christensen, Jennaya; Eyolfson, Eric; Salberg, Sabrina; Mychasiuk, Richelle

doi:10.1016/j.dr.2020.100943

Cited by 12 publications

(16 citation statements)

References 208 publications

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“…Traumatic brain injury (TBI) is caused by external mechanical force or head penetration and can disrupt the homeostasis of the central nervous system (CNS) and cause primary and secondary damage (Al‐Thani et al, 2014; McDonald et al, 2016; Sharp et al, 2014). The severity of the injury, the time that has elapsed since the injury, and the age at which injury occurred all contribute to the effect of TBI on individual patients (Christensen et al, 2021; Early et al, 2020). Astrocytes, which are widely distributed in the CNS, can sense neural activity, regulate homeostasis, and maintain neurophysiological function (Anderson & Swanson, 2000; Jha et al, 2018; Perez‐Catalan et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Specific knockout of Sox2 in astrocytes reduces reactive astrocyte formation and promotes recovery after early postnatal traumatic brain injury in mouse cortex

Liu

Hong

Gong

et al. 2022

Glia

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In response to central nervous system (CNS) injury, astrocytes go through a series of alterations, referred to as reactive astrogliosis, ranging from changes in gene expression and cell hypertrophy to permanent astrocyte borders around stromal cell scars in CNS lesions. The mechanisms underlying injury-induced reactive astrocytes in the adult CNS have been extensively studied. However, little is known about injuryinduced reactive astrocytes during early postnatal development. Astrocytes in the mouse cortex are mainly produced through local proliferation during the first 2 weeks after birth. Here we show that Sox2, a transcription factor critical for stem cells and brain development, is expressed in the early postnatal astrocytes and its expression level was increased in reactive astrocytes after traumatic brain injury (TBI) at postnatal day (P) 7 in the cortex. Using a tamoxifen-induced hGFAP-CreERT2; Sox2 flox/flox ; Rosa-tdT mouse model, we found that specific knockout of Sox2 in astrocytes greatly inhibited the proliferation of reactive astrocytes, the formation of glia limitans borders and subsequently promoted the tissue recovery after postnatal TBI at P7 in the cortex. In addition, we found that injury-induced glia limitans borders were still formed at P2 in the wild-type mouse cortex, and knockout of Sox2 in astrocytes inhibited the reactivity of both astrocytes and microglia. Together, these findings provide evidence that Sox2 is essential for the reactivity of astrocytes in response to the cortical TBI during the early postnatal period and suggest that Sox2-dependent astrocyte reactivity is a potential target for therapeutic treatment after TBI.

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Section: Introductionmentioning

confidence: 99%

Specific knockout of Sox2 in astrocytes reduces reactive astrocyte formation and promotes recovery after early postnatal traumatic brain injury in mouse cortex

Liu

Hong

Gong

et al. 2022

Glia

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“…However, the number of effect sizes was too limited to confirm the moderating effect of prior concussion history. Older age as a risk factor for academic outcomes may have multiple explanations 92,93 . First, coursework in high school and college is more demanding than elementary school and formal grades and testing are conducted with greater frequency.…”

Section: Discussionmentioning

confidence: 99%

“…Other differences between younger and adolescent-aged students have been suggested to be based on hormonal factors as well. 92,93 Additionally, younger students may rely on their parents' knowledge and care-seeking attitudes compared to older students when reporting and treating a concussion. 94 It may also be that because younger students are currently underrepresented in the literature, 48,80 effects in this group have been obscured.…”

Section: Contributors To Postconcussion Academic Outcomesmentioning

confidence: 99%

Investigating the Student in Returning to Learn After Concussion: A Systematic Review and Meta‐Analysis

Kemp

O’Brien

2023

Journal of School Health

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PURPOSE:Examine concussion effects on academic outcomes, including student perspectives. METHODS:This study included a systematic review and meta-analysis examining post-concussion school attendance, academic performance, perceptions of academic difficulty, and accommodations for students in elementary through college settings. The analysis considered pre-and post-injury factors, along with injury factors that contribute to post-concussion academic outcomes. RESULTS:The systematic review showed that students with concussion miss more school days and perceive higher levels of academic difficulty, but results about academic performance varied. Meta-analysis yielded small concussion effects on school absence and academic performance and moderate effects on perceptions of academic difficulty. Female sex, older age, history of migraine, prior concussions, severe or persistent symptoms, vestibular-ocular motor, and cognitive disruptions are risk factors, but these moderators were not identified in the meta-analysis due to lack of effect sizes. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY:This study confirmed negative concussion effects on academic absences, performance, and perceptions of academic difficulty. Identified contributing factors will guide future practices to support students returning to learn after concussion. CONCLUSIONS:Negative impacts to academics from concussion may be amplified by complicating factors. Future investigations are needed to confirm risk factors and mitigating effects of early identification and post-injury supports.

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“…This is particularly true since repeated-mTBIs (r-mTBI) early in life may underlie more serious degenerative disorders later in life, including dementia's, Alzheimer's disease, and Parkinson's disease [7][8][9] . Currently sex differences in the underlying pathophysiology of mTBI are poorly understood, in part due to the majority of preclinical models focusing on adult males 10,11 , ,and the use of animal models that tend to produce more severe injuries than normally occur with mTBI 12 .…”

Section: Introductionmentioning

confidence: 99%

Repeated Mild Traumatic Brain Injury Causes Sex-specific Increases in Cell Proliferation and Inflammation in Juvenile Rats

Neale

Reid

Sousa

et al. 2023

Preprint

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Childhood represents a period of significant growth and maturation for the brain, and is also associated with a heightened risk for mild traumatic brain injuries (mTBI). There is also concern that repeated-mTBI (r-mTBI) may have a long-term impact on developmental trajectories. Using an awake closed head injury (ACHI) model, that uses rapid head acceleration to induce a mTBI, we investigated the acute effects of repeated mTBI (r-mTBI) on neurological function and cellular proliferation in juvenile male and female Long Evans rats. We found that r-mTBI did not lead to cumulative neurological deficits with the model. R-mTBI animals exhibited an increase in BrdU+ (bromodeoxyuridine positive) cells in the dentate gyrus (DG), and that this increase was more robust in male animals. This increase was not sustained, and cell proliferation returning to normal by PID3. A greater increase in BrdU+ cells was observed in the dorsal DG in both male and female r-mTBI animals at PID1. Using Ki-67 expression as an endogenous marker of cellular proliferation, a robust proliferative response following r-mTBI was observed in male animals at PID1 that persisted until PID3, and was not constrained to the DG alone. Triple labeling experiments (Iba1+, GFAP+, Brdu+) revealed that a high proportion of these proliferating cells were microglia/macrophages, indicating there was a heightened inflammatory response. Overall, these findings suggest that rapid head acceleration with the ACHI model produces an mTBI, but that the acute neurological deficits do not increase in severity with repeated administration. R-mTBI transiently increases cellular proliferation in the hippocampus, particularly in male animals, and the pattern of cell proliferation suggests that this represents a neuroinflammatory response that is focused around the mid-brain rather than peripheral cortical regions. These results add to growing literature indicating sex differences in proliferative and inflammatory responses between females and males. Targeting proliferation as a therapeutic avenue may help reduce the short term impact of r-mTBI, but there may be sex-specific considerations.

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Traumatic brain injury in adolescence: A review of the neurobiological and behavioural underpinnings and outcomes

Cited by 12 publications

References 208 publications

Specific knockout of Sox2 in astrocytes reduces reactive astrocyte formation and promotes recovery after early postnatal traumatic brain injury in mouse cortex

Specific knockout of Sox2 in astrocytes reduces reactive astrocyte formation and promotes recovery after early postnatal traumatic brain injury in mouse cortex

Investigating the Student in Returning to Learn After Concussion: A Systematic Review and Meta‐Analysis

Repeated Mild Traumatic Brain Injury Causes Sex-specific Increases in Cell Proliferation and Inflammation in Juvenile Rats

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