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

Abstract

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.

Landscape of gut mucosal immune cells showed gap of follicular or memory B cells into plasma cells in immunological non‐responders

“…34 Collectively, the decrease in gut IGKC + IgA + plasma cell levels in INRs may further diminish IgA production and delay the restoration of the gut mucosal barrier, thereby promoting host immune overactivation and microbial translocation. The gut microbiome plays a key role in the gut-brain axis, 43,44 and whether Prevotellaceae is associated with neurodamage in INRs must be explored. In addition, in untreated chronic PLWH, ILCs may lead to intestinal mucosal inflammation and epithelial barrier disruption, which differs from the conditions in the current study in that there is a decrease in IgA + plasma levels, and this difference may potentially be attributed to the disruption of the intestinal microenvironment 45 and the difference in the patients enrolled.…”

Acute stress modulates the outcome of traumatic brain injury‐associated gene expression and behavioral responses

“…Taken together, this study emphasizes the importance of analyzing sex‐specific behavioral responses, which is currently missing in the majority of reports. Of note, besides sex‐specific differences it will be important that future studies also investigate rodent models of pediatric TBI since young children (0–4 years old) and adolescents (15–19 years old) are the age group most frequently affected by TBI 69 …”

Anti-Inflammatory and Cortical Responses after Transcranial Direct Current Stimulation in Disorders of Consciousness: An Exploratory Study

“…To better characterise the pathophysiology of DOC and to identify potential biomarkers of severity and prognosis, numerous preclinical animal models (e.g., head-open and head-closed injury models) have been developed and, among the many aspects assessed (e.g., behavioural, neuroimaging), a great deal of interest is directed towards biomarkers [ 49 ]. In particular, nonspecific biomarkers, including those for damage (autophagy or apoptosis), inflammation (proinflammatory and anti-inflammatory cytokines), metabolic changes, and degeneration (nerve growth factor, vascular endothelial growth factor, tau protein) seem very promising [ 50 ]. While a fair amount of data are available on these animal models, the evidence on humans is still inconclusive due to the extreme heterogeneity that characterises DOC patients.…”