Juvenile traumatic brain injury

Endoplasmic reticulum (ER) stress and neuroinflammation play an important role in secondary brain damage after traumatic brain injury (TBI). Due to the complex brain cytoarchitecture, multiple cell types are affected by TBI. However, cell type-specific and sex-specific responses to ER stress and neuroinflammation remain unclear. Here we investigated differential regulation of ER stress and neuroinflammatory pathways in neurons and microglia during the acute phase post-injury in a mouse model of impact acceleration TBI in both males and females...

Traumatic brain injury (TBI) is one of the leading causes of death and disability. TBI is associated with neuroinflammation, but temporal changes in immune and inflammatory signaling following TBI have not been fully elucidated. Furthermore, there have been no previous studies on changes in immune cell populations following TBI via the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA). The current study aimed to determine the time course changes to inflammatory marker mRNA expression in the acute period following TBI in juvenile rats and to determine acute changes to brain and circulating immune cell populations...

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Traumatic brain injury (TBI) is a common cause of morbidity and mortality in children. We have previously shown that TBI with a concurrent extra-cranial injury reliably leads to post-injury suppression of the innate and adaptive immune systems. In patients with post-injury immune suppression, if immune function could be preserved, this might represent a therapeutic opportunity. As such, we examined, in an animal injury model, whether systemic administration of GM-CSF could reverse post-injury immune suppression and whether treatment was associated with neuroinflammation or functional deficit...

Studying the properties of neural stem progenitor cells (NSPCs) in a fish model will provide new information about the organization of neurogenic niches containing embryonic and adult neural stem cells, reflecting their development, origin cell lines and proliferative dynamics. Currently, the molecular signatures of these populations in homeostasis and repair in the vertebrate forebrain are being intensively studied. Outside the telencephalon, the regenerative plasticity of NSPCs and their biological significance have not yet been practically studied...

In adult fish, neurogenesis occurs in many areas of the brain, including the cerebellum, with the ratio of newly formed cells relative to the total number of brain cells being several orders of magnitude greater than in mammals. Our study aimed to compare the expressions of aromatase B (AroB), glutamine synthetase (GS), and cystathionine-beta-synthase (CBS) in the cerebellum of intact juvenile chum salmon, Oncorhynchus keta . To identify the dynamics that determine the involvement of AroB, GS, and CBS in the cellular mechanisms of regeneration, we performed a comprehensive assessment of the expressions of these molecular markers during a long-term primary traumatic brain injury (TBI) and after a repeated acute TBI to the cerebellum of O...

Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB), which may exacerbate neuroinflammation post-injury. Few translational studies have examined BBB dysfunction and subsequent neuroinflammation post-TBI in juveniles. We hypothesized that BBB dysfunction positively predicts microglial activation and that vulnerability to BBB dysfunction and associated neuroinflammation are dependent on age at injury. Post-natal day (PND)17 and PND35 rats ( n  = 56) received midline fluid percussion injury or sham surgery, and immunoglobulin-G (IgG) stain was quantified as a marker of extravasated blood in the brain and BBB dysfunction...

Traumatic brain injury (TBI) is a leading cause of disability and increases the risk of developing neurodegenerative diseases. The mechanisms linking TBI to neurodegeneration remain to be defined. It has been proposed that the induction of cellular senescence after injury could amplify neuroinflammation and induce long-term tissue changes. The induction of a senescence response post-injury in the immature brain has yet to be characterised. We carried out two types of brain injury in juvenile CD1 mice: invasive TBI using controlled cortical impact (CCI) and repetitive mild TBI (rmTBI) using weight drop injury...

INTRODUCTION: The sensitivity of white matter (WM) in acute and chronic moderate-severe traumatic brain injury (TBI) has been established. In concussion syndromes, particularly in preclinical rodent models, there is lacking a comprehensive longitudinal study spanning the lifespan of the mouse. We previously reported early modifications to WM using clinically relevant neuroimaging and histological measures in a model of juvenile concussion at one month post injury (mpi) who then exhibited cognitive deficits at 12mpi...

The gut-brain axis interconnects the CNS and the commensal bacteria of the gastrointestinal tract. The composition of the diet consumed by the host influences the richness of the microbial populations. Traumatic brain injury (TBI) produces profound neurocognitive damage, but it is unknown how diet influences the microbiome following TBI. The present work investigates the impact of a chow diet vs. a 60% fat diet (HFD) on fecal microbiome populations in juvenile rats following TBI. Twenty-day-old male rats were placed on one of two diets for 9 days before sustaining either a Sham or TBI via the CHIMERA...

Childhood represents a period of significant growth and maturation for the brain, and is also associated with a heightened risk for mild traumatic brain injuries (mTBI). There is also concern that repeated-mTBI (r-mTBI) may have a long-term impact on developmental trajectories. Using an awake closed head injury (ACHI) model, that uses rapid head acceleration to induce a mTBI, we investigated the acute effects of repeated-mTBI (r-mTBI) on neurological function and cellular proliferation in juvenile male and female Long-Evans rats...

Objective: To explore the clinical characteristics and treatment outcomes of patients with lightning injury on plateau in Tibet Autonomous Region, and to analyze the risk factors for heart injuries in these patients. Methods: A retrospective case series study was conducted. From January 2008 to July 2023, 55 patients with lightning injury who met the inclusion criteria were admitted to the General Hospital of PLA Tibet Military Area Command. The gender, age, ethnicity, time of injury, location of injury (average altitude), activity at the time of injury, the occurrence of thermal burns on the body surface, the occurrence of complication, the occurrence of combined injury, underlying disease or physiological process before injury, length of hospital stay, treatment outcome, and effective rate of treatment were recorded...

Early life stress (ELS) affects neurogenesis, cognitive performance, and increases neuroinflammation after a pediatric mild traumatic brain injury (mTBI). Previous studies have shown that ELS has minimal effects in juveniles, but it shows an age-dependent effect in adults. Hence, we aimed to evaluate if ELS affects cognitive performance, hippocampal microglial activation, and neurogenesis after a mTBI in adult male rats. Maternal separation for 180 min per day (MS180) during the first 21 post-natal (P) days was used as an ELS model, while controls (CONT) remained undisturbed...

Traumatic brain injury (TBI) can damage the hypothalamus and cause improper activation of the growth hormone (GH)-axis, leading to growth hormone deficiency (GHD). GHD is one of the most prevalent endocrinopathies following TBI in adults; however, the extent to which GHD affects juveniles remains understudied. We used post-natal day 17 rats (n = 83), which model the late infantile/toddler period, and assessed body weights, GH levels, and number of hypothalamic somatostatin neurons at acute (1, 7 days post-injury; DPI) and chronic (18, 25, 43 DPI) time points...

BACKGROUND: Recurrent non-epileptic episodes of frightened facial and body expression occur in more than half of post-adolescent patients with juvenile neuronal ceroid lipofuscinosis (JNCL, CLN3 disease). Clinically, the episodes look similar to the attacks of paroxysmal sympathetic hyperactivity (PSH) commonly seen following traumatic brain injury (TBI). The episodes occur when the patients are exposed to separation, hear loud sounds or are otherwise bothered by discomfort and as in PSH following TBI, the attacks are difficult to prevent and/or treat...

Background and Objectives : Higher level of aggression and antisocial behavior have been found in the period following head trauma. These changes are attributable to specific brain alterations that generally involved frontal lobe, insula and limbic system. A descriptive review was conducted on the specificity of aggressive behavior in relation to traumatic brain injury by evaluating numerous variables, focusing on age at the time of trauma and neuroimaging studies. Materials and Methods : We searched on PubMed and the Web of Science databases to screen references of included studies and review articles for additional citations...

Maternal opioid use poses a significant health concern not just to the expectant mother but also to the fetus. Notably, increasing numbers of children born suffering from neonatal opioid withdrawal syndrome (NOWS) further compounds the crisis. While epidemiological research has shown the heightened risk factors associated with NOWS, little research has investigated what molecular mechanisms underly the vulnerabilities these children carry throughout development and into later life. To understand the implications of in utero and post-natal opioid exposure on the developing brain, we sought to assess the response to one of the most common pediatric injuries: minor traumatic brain injury (mTBI)...

The mechanical role of the skull-brain interface is critical to the pathology of concussion and traumatic brain injury (TBI) and may evolve with age. Here we characterize the skull-brain interface in juvenile, female Yucatan mini-pigs from 3 to 6 months old using techniques from magnetic resonance elastography (MRE). The displacements of the skull and brain were measured by a motion-sensitive MR imaging sequence during low-amplitude harmonic motion of the head. Each animal was scanned four times at 1-month intervals...

BACKGROUND: Juvenile neuronal ceroid lipofuscinosis (JNCL, CLN3) is a childhood-onset neurodegenerative disease with prominent symptoms comprising a pediatric dementia syndrome. As in adult dementia, behavioral symptoms like mood disturbances and anxiety are common. In contrast to in adult dementia, however, the anxious behavioral symptoms increase during the terminal phase of JNCL disease. In the present study, the current understanding of the neurobiological mechanisms of anxiety and anxious behavior in general is addressed as will a discussion of the mechanism of the anxious behavior seen in young JNCL patients...

The arachidonic acid pathway metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) contributes to ischemia/reperfusion brain injury. Inhibition of 20-HETE formation can protect the developing brain from global ischemia. In previous studies, we have found that treatment with the 20-HETE synthesis inhibitor N-hydroxy-N-4-butyl-2-methylphenylformamidine (HET0016) can protect the immature brain from traumatic brain injury (TBI), but its hydrophobic nature limits its full potential. We designed a reactive oxygen species-responsive HET0016 prodrug, which consists of a thioketal link between HET0016 and stearyl alcohol (HET-TK-SA), and used the nanoprodrug strategy to successfully synthesize liposomes HET0016 prodrug liposomes (HPLs) to facilitate the application of HET0016 in protection from TBI...