Clinical Updates in Mild Traumatic Brain Injury (Concussion)

Moore, Megan; Sandsmark, Danielle K.

doi:10.1016/j.nic.2023.01.003

Cited by 5 publications

(3 citation statements)

References 32 publications

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“…Additionally, the microenvironment and biology of cells may affect the content of exosomes and their biological markers. Exosomes can carry membrane proteins, cytosolic and nuclear proteins, extracellular matrix proteins, metabolites, and nucleic acids, such as mRNA, noncoding RNA species, and DNA [ 1 , 10 , 11 , 12 ]. Although exosomal cargo analyses require large pools of purified exosomes, the abundance of a given cargo in exosomes can differ, as shown by miRNA exosomal cargo [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Microglial Exosomes and miR-124-3p in Neuroinflammation and Neuronal Repair after Traumatic Brain Injury

Mavroudis,

Balmus,

Ciobica

et al. 2023

Life

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(1) Background: In this study, we aimed to explore the regulatory mechanism of miR-124-3p microglial exosomes, as they were previously reported to modulate neuroinflammation and promote neuronal repair following traumatic brain injury (TBI). (2) Methods: Studies investigating the impact of microglial exosomal miRNAs, specifically miR-124-3p, on injured neurons and brain microvascular endothelial cells (BMVECs) in the context of TBI were reviewed. (3) Results: Animal models of TBI, in vitro cell culture experiments, RNA sequencing analysis, and functional assays were employed to elucidate the mechanisms underlying the effects of miR-124-3p-loaded exosomes on neuroinflammation and neuronal repair. Anti-inflammatory M2 polarization of microglia, mTOR signaling suppression, and BMVECs-mediated autophagy were reported as the main processes contributing to neuroprotection, reduced blood-brain barrier leakage, and improved neurologic outcomes in animal models of TBI. (4) Conclusions: Microglial exosomes, particularly those carrying miR-124-3p, have emerged as promising candidates for therapeutic interventions in TBI. These exosomes exhibit neuroprotective effects, attenuate neuroinflammation, and promote neuronal repair and plasticity. However, further research is required to fully elucidate the underlying mechanisms and optimize their delivery strategies for effective treatment in human TBI cases.

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Section: Introductionmentioning

confidence: 99%

The Role of Microglial Exosomes and miR-124-3p in Neuroinflammation and Neuronal Repair after Traumatic Brain Injury

Mavroudis,

Balmus,

Ciobica

et al. 2023

Life

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“…Each year more than 55 million people, worldwide, are estimated to experience a mild TBI and 5.5 million a severe TBI [ 2 ]. The most recent data from the CDC, published in 2019, estimates 2.87 million emergency department visits, hospitalizations, and deaths in the United States, annually, related to TBI [ 3 ]. Data suggest that some groups of people are at greater risk of death from a TBI or experiencing long-term neurological problems after injury [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Intranasal human-recombinant NGF administration improves outcome in children with post-traumatic unresponsive wakefulness syndrome

Gatto,

Capossela,

Conti

et al. 2023

Biol Direct

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Background Severe traumatic brain injury (TBI) is one of the most dramatic events in pediatric age and, despite advanced neuro-intensive care, the survival rate of these patients remains low. Children suffering from severe TBI show long-term sequelae, more pronounced in behavioral, neurological and neuropsychological functions leading to, in the most severe cases, an unresponsive wakefulness syndrome (UWS). Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. In experimental animal models, human- recombinant Nerve Growth Factor (hr-NGF) promotes neural recovery supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated processes. Only a few studies reported the efficacy of intranasal hr-NGF administration in children with post- traumatic UWS. Methods Children with the diagnosis of post-traumatic UWS were enrolled. These patients underwent a treatment with intranasal hr-NGF administration, at a total dose of 50 gamma/kg, three times a day for 7 consecutive days. The treatment schedule was performed for 4 cycles, at one month distance each. Neuroradiogical evaluation by Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG), and Power Spectral Density (PSD) was determined before the treatment and one month after the end. Neurological assessment was also deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale. Results Three children with post-traumatic UWS were treated. hr-NGF administration improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary movements, facial mimicry, attention and verbal comprehension, ability to cry, cough reflex, oral motility, and feeding capacity, with a significant improvement of their neurological scores. No side effects were reported. Conclusion These promising results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from severe TBI and in patients with better baseline neurological conditions, to explore more thoroughly the benefits of this new approach on neuronal function recovery after traumatic brain damage.

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“…In the case of severe and moderate TBI, the various pathobiological changes occur in a partly overlapping fashion but the intensities and temporal pattern of the individual process differ and these processes interact in a highly complex fashion, such that one may trigger another [46,64,65]. Mild TBI on the other hand only causes temporary perturbance of cellular structures, and may dislocate membrane-bound ion channels, receptors and/or intracellular organelles, causing typically transient molecular disturbances reflected in metabolic abnormalities that clinically manifest as a temporary altered state of consciousness [34,51,[66][67][68]. Complicated mild TBI, a subcategory that can be clinically defined as prolonged symptoms or an absence of full recovery [69][70][71], is caused by more severe mechanical damage to cells, and protracted disruption of neuronal signaling due to network disruptions [69,72].…”

Section: Introductionmentioning

confidence: 99%

Fluid-Based Protein Biomarkers in Traumatic Brain Injury: The View from the Bedside

Agoston,

Helmy

2023

IJMS

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There has been an explosion of research into biofluid (blood, cerebrospinal fluid, CSF)-based protein biomarkers in traumatic brain injury (TBI) over the past decade. The availability of very large datasets, such as CENTRE-TBI and TRACK-TBI, allows for correlation of blood- and CSF-based molecular (protein), radiological (structural) and clinical (physiological) marker data to adverse clinical outcomes. The quality of a given biomarker has often been framed in relation to the predictive power on the outcome quantified from the area under the Receiver Operating Characteristic (ROC) curve. However, this does not in itself provide clinical utility but reflects a statistical association in any given population between one or more variables and clinical outcome. It is not currently established how to incorporate and integrate biofluid-based biomarker data into patient management because there is no standardized role for such data in clinical decision making. We review the current status of biomarker research and discuss how we can integrate existing markers into current clinical practice and what additional biomarkers do we need to improve diagnoses and to guide therapy and to assess treatment efficacy. Furthermore, we argue for employing machine learning (ML) capabilities to integrate the protein biomarker data with other established, routinely used clinical diagnostic tools, to provide the clinician with actionable information to guide medical intervention.

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Clinical Updates in Mild Traumatic Brain Injury (Concussion)

Cited by 5 publications

References 32 publications

The Role of Microglial Exosomes and miR-124-3p in Neuroinflammation and Neuronal Repair after Traumatic Brain Injury

The Role of Microglial Exosomes and miR-124-3p in Neuroinflammation and Neuronal Repair after Traumatic Brain Injury

Intranasal human-recombinant NGF administration improves outcome in children with post-traumatic unresponsive wakefulness syndrome

Fluid-Based Protein Biomarkers in Traumatic Brain Injury: The View from the Bedside

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