Pediatric Traumatic Brain Injury: Impact on the Developing Brain

Blackwell, Laura S.; Grell, Robert M

doi:10.1016/j.pediatrneurol.2023.06.019

Cited by 4 publications

(1 citation statement)

References 117 publications

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“…According to the CDC’s latest reports from 2021, there were 69,413 TBI-related deaths, and nearly 2500 of those were children or adolescents. Children and teenagers are particularly vulnerable to head injuries, as the sequelae of TBI disrupt normal neurocognitive and behavioral development [ 43 ]. While public awareness of concussions, TBI, and their dangers has grown significantly, there are still no effective clinical options to treat patients of all ages [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Engineered Dual Antioxidant Enzyme Complexes Targeting ICAM-1 on Brain Endothelium Reduce Brain Injury-Associated Neuroinflammation

Leonard,

Shuvaev,

Bullock

et al. 2024

Bioengineering

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The neuroinflammatory cascade triggered by traumatic brain injury (TBI) represents a clinically important point for therapeutic intervention. Neuroinflammation generates oxidative stress in the form of high-energy reactive oxygen and nitrogen species, which are key mediators of TBI pathology. The role of the blood–brain barrier (BBB) is essential for proper neuronal function and is vulnerable to oxidative stress. Results herein explore the notion that attenuating oxidative stress at the vasculature after TBI may result in improved BBB integrity and neuroprotection. Utilizing amino-chemistry, a biological construct (designated “dual conjugate” for short) was generated by covalently binding two antioxidant enzymes (superoxide dismutase 1 (SOD-1) and catalase (CAT)) to antibodies specific for ICAM-1. Bioengineering of the conjugate preserved its targeting and enzymatic functions, as evaluated by real-time bioenergetic measurements (via the Seahorse-XF platform), in brain endothelial cells exposed to increasing concentrations of hydrogen peroxide or a superoxide anion donor. Results showed that the dual conjugate effectively mitigated the mitochondrial stress due to oxidative damage. Furthermore, dual conjugate administration also improved BBB and endothelial protection under oxidative insult in an in vitro model of TBI utilizing a software-controlled stretching device that induces a 20% in mechanical strain on the endothelial cells. Additionally, the dual conjugate was also effective in reducing indices of neuroinflammation in a controlled cortical impact (CCI)-TBI animal model. Thus, these studies provide proof of concept that targeted dual antioxidant biologicals may offer a means to regulate oxidative stress-associated cellular damage during neurotrauma.

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Section: Discussionmentioning

confidence: 99%

Engineered Dual Antioxidant Enzyme Complexes Targeting ICAM-1 on Brain Endothelium Reduce Brain Injury-Associated Neuroinflammation

Leonard,

Shuvaev,

Bullock

et al. 2024

Bioengineering

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Pediatric Traumatic Brain Injury: Models, Therapeutics, and Outcomes

Moschonas,

Annas,

Zamudio-Flores

et al. 2024

Advances in Neurobiology

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Transient Increases in Alpha Power Relative to Healthy Reference Ranges in Awake Piglets After Repeated Rapid Head Rotations

Oeur,

Torp,

Margulies

2024

Biomedicines

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Background/Objectives: Sports-related concussions are a main cause of cognitive dysfunction and somatic complaints, particularly in youth. While the majority of concussion symptoms resolve within one week, cognitive effects may persist. In this study, we sought to study changes to cognition within this acute time frame. Methods: In this current study, we use an established swine model of traumatic brain injury (TBI) to study the effects of single and repeated head rotations on resting-state electroencephalography (rs-EEG) in awake piglets in the acute (within 7 days) time period after injury. We studied both healthy and experimental groups to (1) establish healthy reference ranges (RRs; N = 23) for one-minute rs-EEG in awake piglets, (2) compare the effects of single (N = 12) and repeated head rotations (N = 13) on rs-EEG, and (3) examine the acute time course (pre-injury and days 1, 4, and 7 post-injury) in animals administered single and repeated head rotations. EEG data were Fourier transformed, and total (1–30 Hz) and relative power in the alpha (8–12 Hz), beta (16.5–25 Hz), delta (1–4 Hz), and theta (4–7.5 Hz) bands were analyzed. Results: Total power and relative alpha, beta, delta, and theta power were consistent measures across days in healthy animals. We found a significant and transient increase in relative alpha power after repeated injury on day 1 in all regions and a rise above the healthy RR in the frontal and left temporal regions. Conclusions: Future studies will expand the study duration to investigate and inform clinical prognoses from acute measurements of rs-EEG.

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Pediatric Traumatic Brain Injury: Impact on the Developing Brain

Cited by 4 publications

References 117 publications

Engineered Dual Antioxidant Enzyme Complexes Targeting ICAM-1 on Brain Endothelium Reduce Brain Injury-Associated Neuroinflammation

Engineered Dual Antioxidant Enzyme Complexes Targeting ICAM-1 on Brain Endothelium Reduce Brain Injury-Associated Neuroinflammation

Pediatric Traumatic Brain Injury: Models, Therapeutics, and Outcomes

Transient Increases in Alpha Power Relative to Healthy Reference Ranges in Awake Piglets After Repeated Rapid Head Rotations

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