Pathophysiology of Pediatric Traumatic Brain Injury

Serpa, Rebecka; Ferguson, Lindsay; Jr., C. P. Larson; Bailard, Julie; Cooke, Samantha; Greco, Tiffany; Prins, Mayumi L.

doi:10.3389/fneur.2021.696510

Cited by 31 publications

(10 citation statements)

References 194 publications

(197 reference statements)

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“…This suggests that impairments in maximum finger strength may develop as a function of time (as time since injury is longer in the CP group) and follow a different trajectory to fine motor control of the hand. Additionally, the differences between the findings for the MVC and the functional tests suggest that the impairment in performing these tests is a result of deficits in finger control rather than of finger strength, it may also be due to cognitive effects ( Fluss and Lidzba, 2020 ; Serpa et al, 2021 ) such as attention or motivation deficits ( Marin and Wilkosz, 2005 ; Salavati et al, 2018 ) in these populations.…”

Section: Discussionmentioning

confidence: 98%

Developmental and acquired brain injury have opposite effects on finger coordination in children

Mimouni-Bloch

Shaklai

Levin

et al. 2023

Front. Hum. Neurosci.

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The ability to coordinate finger forces to dexterously perform tasks develops in children as they grow older. Following brain injury, either developmental (as in cerebral palsy–CP) or acquired (as in traumatic brain injury—TBI), this developmental trajectory will likely be impaired. In this study, we compared finger coordination in a group of children aged 4–12 with CP and TBI to a group of typically developing children using an isometric pressing task. As expected, deficits were observed in functional tests (Jebsen Taylor test of hand function, Box and Block test) for both groups, and children in both groups performed the pressing task less well than the control group. However, differing results were observed between the CP and TBI groups when using the uncontrolled manifold hypothesis to look at the synergy index. This index measures the relative amount of “good” (does not affect the outcome measure) and “bad” (does affect the outcome measure) variability, where in this case the outcome measure is the total force produced by the fingers. While children with CP were more variable in their performance, their synergy index was not significantly different from typically developing children, suggesting the development of compensatory strategies. In contrast, the children following TBI showed performance that got worse as a function of age (i.e., the older children with TBI performed worse than the younger children with TBI). These differences between the groups may be a result of different areas of brain injury typically observed in CP and TBI, and the different amount of time that has passed since the injury.

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Section: Discussionmentioning

confidence: 98%

Developmental and acquired brain injury have opposite effects on finger coordination in children

Mimouni-Bloch

Shaklai

Levin

et al. 2023

Front. Hum. Neurosci.

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“…Only one publication [ 153 ] used juvenile rats as a model for a TMS study. Since TBI is the disease with one of the highest incidences in children and youth below 19 years old [ 207 ], it is of utmost importance to further encourage studies employing neurostimulation methods as a post-traumatic therapy in young animals, with special focus on non-invasive methods.…”

Section: Discussionmentioning

confidence: 99%

Electrical stimulation methods and protocols for the treatment of traumatic brain injury: a critical review of preclinical research

Ziesel

Nowakowska

Scheruebel

et al. 2023

J NeuroEngineering Rehabil

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Background Traumatic brain injury (TBI) is a leading cause of disabilities resulting from cognitive and neurological deficits, as well as psychological disorders. Only recently, preclinical research on electrical stimulation methods as a potential treatment of TBI sequelae has gained more traction. However, the underlying mechanisms of the anticipated improvements induced by these methods are still not fully understood. It remains unclear in which stage after TBI they are best applied to optimize the therapeutic outcome, preferably with persisting effects. Studies with animal models address these questions and investigate beneficial long- and short-term changes mediated by these novel modalities. Methods In this review, we present the state-of-the-art in preclinical research on electrical stimulation methods used to treat TBI sequelae. We analyze publications on the most commonly used electrical stimulation methods, namely transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS) and vagus nerve stimulation (VNS), that aim to treat disabilities caused by TBI. We discuss applied stimulation parameters, such as the amplitude, frequency, and length of stimulation, as well as stimulation time frames, specifically the onset of stimulation, how often stimulation sessions were repeated and the total length of the treatment. These parameters are then analyzed in the context of injury severity, the disability under investigation and the stimulated location, and the resulting therapeutic effects are compared. We provide a comprehensive and critical review and discuss directions for future research. Results and conclusion We find that the parameters used in studies on each of these stimulation methods vary widely, making it difficult to draw direct comparisons between stimulation protocols and therapeutic outcome. Persisting beneficial effects and adverse consequences of electrical simulation are rarely investigated, leaving many questions about their suitability for clinical applications. Nevertheless, we conclude that the stimulation methods discussed here show promising results that could be further supported by additional research in this field.

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“…Herein, we used morphological changes in both microglia and astrocytes as physical indicators of distress, damage, and/or inflammation in the cortex of the brain, whereby reduced ramification was an indicator of microglial activation. Few pre-clinical models have examined TBI-associated pathology in juvenile rats ( 8 ). Therefore, we used a comprehensive time course after experimental TBI in rats to examine the acute and sub-acute cortical glial response (microglial activation and GFAP expression) to TBI.…”

Section: Introductionmentioning

confidence: 99%

“…Little is known about the specific glial response to TBI acquired as a toddler or an adolescent, which are two unique time periods for brain development. Support exists for these developmental periods being windows of both neuroprotection and increased vulnerability, phenomena that are likely mutually exclusive (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Age-At-Injury Influences the Glial Response to Traumatic Brain Injury in the Cortex of Male Juvenile Rats

et al. 2022

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Few translational studies have examined how age-at-injury affects the glial response to traumatic brain injury (TBI). We hypothesized that rats injured at post-natal day (PND) 17 would exhibit a greater glial response, that would persist into early adulthood, compared to rats injured at PND35. PND17 and PND35 rats (n = 75) received a mild to moderate midline fluid percussion injury or sham surgery. In three cortical regions [peri-injury, primary somatosensory barrel field (S1BF), perirhinal], we investigated the glial response relative to age-at-injury (PND17 or PND35), time post-injury (2 hours, 1 day, 7 days, 25 days, or 43 days), and post-natal age, such that rats injured at PND17 or PND35 were compared at the same post-natal-age (e.g., PND17 + 25D post-injury = PND42; PND35 + 7D post-injury = PND42). We measured Iba1 positive microglia cells (area, perimeter) and quantified their activation status using skeletal analysis (branch length/cell, mean processes/cell, cell abundance). GFAP expression was examined using immunohistochemistry and pixel analysis. Data were analyzed using Bayesian multivariate multi-level models. Independent of age-at-injury, TBI activated microglia (shorter branches, fewer processes) in the S1BF and perirhinal cortex with more microglia in all regions compared to uninjured shams. TBI-induced microglial activation (shorter branches) was sustained in the S1BF into early adulthood (PND60). Overall, PND17 injured rats had more microglial activation in the perirhinal cortex than PND35 injured rats. Activation was not confounded by age-dependent cell size changes, and microglial cell body sizes were similar between PND17 and PND35 rats. There were no differences in astrocyte GFAP expression. Increased microglial activation in PND17 brain-injured rats suggests that TBI upregulates the glial response at discrete stages of development. Age-at-injury and aging with an injury are translationally important because experiencing a TBI at an early age may trigger an exaggerated glial response.

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Pathophysiology of Pediatric Traumatic Brain Injury

Cited by 31 publications

References 194 publications

Developmental and acquired brain injury have opposite effects on finger coordination in children

Developmental and acquired brain injury have opposite effects on finger coordination in children

Electrical stimulation methods and protocols for the treatment of traumatic brain injury: a critical review of preclinical research

Age-At-Injury Influences the Glial Response to Traumatic Brain Injury in the Cortex of Male Juvenile Rats

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