Traumatic brain injury biomarkers in pediatric patients: a systematic review

Marzano, Lucas Alexandre Santos; Batista, João Pedro Thimotheo; Arruda, Marina De Abreu; Cardoso, Maíra Glória de Freitas; Barros, João Luís Vieira Monteiro de; Moreira, Janaína Matos; Liu, Priscila Menezes Ferri; Teixeira, Antônio Lúcio; Silva, Ana Cristina Simões e; Miranda, Aline Silva de

doi:10.1007/s10143-021-01588-0

Cited by 9 publications

(7 citation statements)

References 103 publications

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“…TBI is a major cause of death in young people under the age of 45 and remains one of the major health and socioeconomic problems worldwide [1][2][3]. Trauma-induced changes in the catalytic activity of enzymes involved in major biochemical cascades lead to neuroinflammation, cognitive dysfunction and increased mortality [4][5][6][7][8], offering potential targets for therapeutic interventions.…”

Section: Article Type: Rapid Communicationsmentioning

confidence: 99%

Activity based proteome profiling of serum serine hydrolases: application in pediatric abusive head trauma

Maret,

Wiskott,

Shipley

et al. 2024

Preprint

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Purpose: Traumatic brain injury (TBI), including pediatric abusive head trauma (AHT), is the leading cause of death and disability in children and young adults worldwide. The current understanding of trauma-induced molecular changes in the brain of human subjects with intracranial haemorrhage (ICH) remains inadequate and requires further investigation to improve the outcome and management of TBI in the clinic. Calcium-mediated damage at the site of brain injury has been shown to activate several catalytic enzymes. Experimental design: Serine hydrolases (SHs) are major catalytic enzymes involved in the biochemical pathways of blood coagulation, systemic inflammation and neuronal signaling. Here we investigated activity-based protein profiling (ABPP) by measuring the activity status of SH enzymes in the serum of infants with severe ICH as a consequence of AHT or atraumatic infants who died of sudden infant death syndrome (SIDS). Results: Our proof-of-principle study revealed significantly reduced physiological activity of dozens of metabolic SHs in the serum of infants with severe AHT compared to the SIDS group, with some of the enzymes being related to neurodevelopment and basic brain metabolism Conclusions and clinical relevance: To our knowledge, this is the first study to investigate the ABPP of the SHs enzyme family to detect changes in their physiological activity in blood serum in severe TBI. We used antemortem (AM) serum from infants under the age of 2 years who were victims of AHT with a severe form of ICH. The analytical approach used in the proof-of-principle study shows reduced activities of serum serine lipases in AHT cases and could be further investigated in mild forms of AHT, which currently show 30% of misdiagnosed cases in clinics.

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Section: Article Type: Rapid Communicationsmentioning

confidence: 99%

Activity based proteome profiling of serum serine hydrolases: application in pediatric abusive head trauma

Maret,

Wiskott,

Shipley

et al. 2024

Preprint

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“…For validation experiments, we prioritize the available sera of respective infants as the gold clinical specimen for quantification of laboratory markers [20]. The serum levels of AHT and atraumatic control infants were determined by ELISA commercial assays for two selected proteins with brain-enhanced expression (Human Brain Abundant, Membrane Attached Signal Protein 1 (BASP1) ELISA Kit, AssayGenie, Dublin, Ireland, and Human Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 (ENPP2) ELISA kit Cusabio, Houston, TX 77054, USA).…”

Section: Validation Of Brain Acid Soluble Protein 1 (Basp1) and Ecton...mentioning

confidence: 99%

Blood proteome of acute intracranial hemorrhage in infant victims of abusive head trauma

et al. 2023

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Abusive head trauma (AHT) is a leading cause of mortality and morbidity in infants.While the reported incidence is close to 40 cases per 100′000 births/year, misdiagnoses are commonly observed in cases with atypical, subacute, or chronic presentation.Currently, standard clinical evaluation of inflicted intracranial hemorrhagic injury (ICH) in infants urgently requires a screening test able to identify infants who need additional investigations. Blood biomarkers characteristic of AHT may assist in detecting these infants, improving prognosis through early medical care. To date, the application of innovative omics technologies in retrospective studies of AHT in infants is rare, due also to the blood serum and cerebrospinal fluid of AHT cases being scarce and not systematically accessible. Here, we explored the circulating blood proteomes of infants with severe AHT and their atraumatic controls. We discovered 165 circulating serum proteins that display differential changes in AHT cases compared with atraumatic controls. The peripheral blood proteomes of pediatric AHT commonly reflect:(i) potentially secreted proteome from injured brain, and (ii) proteome dysregulated in the system's circulation by successive biological events following acute ICH. This study opens up a novel opportunity for research efforts in clinical screening of AHT cases.

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“…For an in-depth discussion on the relevance of pTBI biomarkers, the reader is referred to this excellent review. 150 …”

Section: Neuroimaging and Assessment Of Clinical Biomarkers Following...mentioning

confidence: 99%

“…For an in-depth discussion on the relevance of pTBI biomarkers, the reader is referred to this excellent review. 150 A Putative Role for the Gut-Brain Axis (GBA) in pTBI Pathophysiology…”

Section: Cerebral Blood Flow Dysfunction Following Ptbimentioning

confidence: 99%

Pediatric Traumatic Brain Injury: An Update on Preclinical Models, Clinical Biomarkers, and the Implications of Cerebrovascular Dysfunction

Nwafor

Brichacek

Foster

et al. 2022

J Cent Nerv Syst Dis

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Traumatic brain injury (TBI) is a leading cause of pediatric morbidity and mortality. Recent studies suggest that children and adolescents have worse post-TBI outcomes and take longer to recover than adults. However, the pathophysiology and progression of TBI in the pediatric population are studied to a far lesser extent compared to the adult population. Common causes of TBI in children are falls, sports/recreation-related injuries, non-accidental trauma, and motor vehicle-related injuries. A fundamental understanding of TBI pathophysiology is crucial in preventing long-term brain injury sequelae. Animal models of TBI have played an essential role in addressing the knowledge gaps relating to pTBI pathophysiology. Moreover, a better understanding of clinical biomarkers is crucial to diagnose pTBI and accurately predict long-term outcomes. This review examines the current preclinical models of pTBI, the implications of pTBI on the brain’s vasculature, and clinical pTBI biomarkers. Finally, we conclude the review by speculating on the emerging role of the gut-brain axis in pTBI pathophysiology.

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Traumatic brain injury biomarkers in pediatric patients: a systematic review

Cited by 9 publications

References 103 publications

Activity based proteome profiling of serum serine hydrolases: application in pediatric abusive head trauma

Activity based proteome profiling of serum serine hydrolases: application in pediatric abusive head trauma

Blood proteome of acute intracranial hemorrhage in infant victims of abusive head trauma

Pediatric Traumatic Brain Injury: An Update on Preclinical Models, Clinical Biomarkers, and the Implications of Cerebrovascular Dysfunction

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