Neurotrauma reports最新文献

The objective of this study was to compare participants at-risk for trauma-related neurodegeneration to a healthy control group on outcomes associated with Alzheimer's disease (AD), such as subjective symptoms, neurocognitive performance, plasma biomarkers, volumetrics, amyloid-beta (Aβ) positron emission tomography (PET), and tau PET. Participants completed a comprehensive assessment protocol for neurodegenerative disease, including magnetic resonance imaging (MRI), PET scans for tau and Aβ, blood draw, subjective symptom reports related to neurodegenerative disease, and objective neurocognitive assessment. Surveys included the Neurobehavioral Symptom Inventory (NSI), Insomnia Severity Index (ISI), Epworth Sleepiness Severity (ESS), PTSD Checklist for DSM-5 (PCL-5), Brief Symptom Inventory-18 (BSI-18), Satisfaction with Life Scale (SWLS), Barratt Impulsivity Scale (BIS), and Buss Perry Aggression Questionnaire (BPAQ). PET scans were read by a neuroradiologist and rated positive or negative based upon established cutoffs. General linear models compared participants with TBI history with controls on outcomes. Age, years of education, military status, biological sex, race/ethnicity, and total self-reported TBIs were included as covariates in all models with Bonferroni corrections. Forward stepwise linear regression models were built to associate neuroimaging outcomes with symptom domains; inclusion in the linear regression required a p value <0.1. The average age for both groups was ∼40 years. The TBI group reported an average of five TBIs; the control group reported an average of one TBI. Across seven regions of interest, only one TBI participant met established PET cutoffs for neuropathology in one cortical region. After controlling for age, sex, race/ethnicity, years of education, military status, and TBI history, there were no statistically significant differences between groups in any neurocognitive outcome (p = 0.06-0.95), Aβ or tau PET (p = 0.05-0.70), MRI volumetrics (p = 0.06-0.98), or plasma biomarkers (p = 0.06-0.85). The TBI group had higher NSI, PCL-5, BSI-18, BPAQ, ESS, and ISI scores compared with the controls (p < 0.001-0.042). Within the TBI group, amygdala normative percentile and/or amygdala asymmetry index were included in the final models for NSI, SWLS, PCL5, BIS, BPAQ, and ISI. Only two models included a statistically significant PET outcome in the final model. In this sample with a mean age of 40 and a history of 5+ TBIs, core diagnostic biomarkers for AD were not different from controls despite significantly higher symptom burden. Volumetrics in critical brain regions were associated with several symptom domains in the TBI group, indicating that cortical volumetrics (especially in the amygdala) may be a more viable early biomarker of chronic symptom burden in this population than PET scans.

Approximately 280 children per 100,000 experience closed-head injuries each year, with over 80% being mild in severity. While most children with mild injuries do not require admission to a hospital and recover well over time, some children experience persistent behavioral and cognitive abnormalities that continue into adolescence. Mild traumatic brain injury (mTBI) during early life has potential to disrupt critical developmental processes and lead to long-term consequences; however, the mechanistic underpinnings of mTBI's effects on brain development remain understudied. Here, we investigated the effects of early-life mTBI on developmental outcomes using a mouse model. Injury was induced on post-natal day 7 by a single weight drop of one of three different impact intensities. Injury resulted in significant white matter loss as measured by myelin basic protein immunoreactivity at 5 days post injury (dpi). There was no change in the extent of Iba1-positive microglial staining at 5 dpi; however, there was increased expression of complement signaling proteins responsible for microglial-regulated synaptic pruning during this time in development. To assess the neurological consequences of mTBI, we examined the development of innate behaviors and ultrasonic vocalization communication. Injured mice were slower to achieve developmental milestones and exhibited altered communication, indicating functional deficits associated with mild injury. Altogether, this study provides evidence for neurodevelopmental consequences of mTBI and demonstrates lasting behavioral effects, suggesting further investigation of mechanisms contributing to neurological effects of mild injury in early life is warranted.

Traumatic brain injury (TBI) represents a significant cause of injury-related deaths and disabilities. Repeated exposure to mechanical impact can lead to metabolic and ionic imbalance, which can cause oxidative stress and worsen the cellular dysfunction initiated by the initial mild TBI (mTBI). Currently, no FDA-approved drug targets repeated mTBI (rmTBI) and its potential sequelae. Mitoquinone (MitoQ) is a mitochondrion-targeted drug that has proven beneficial in different brain-related diseases. We have previously demonstrated the neurotherapeutic effects of MitoQ at a 30-day chronic time point in a similar rmTBI mouse model, where we observed decreased neuroinflammation, enhanced behavioral outcomes, and diminished oxidation. Recently, alterations in glycans have been shown to modulate key roles in the nervous system. Their relevance has been recognized in several neurodegenerative disorders, including TBI, which indicated injury severity and pathobiology. In this study, we aimed to assess brain glycome profiles post MitoQ treatment in experimental rmTBI using liquid chromatography-tandem mass spectrometry. Our findings indicate that there is a correlation between the HexNAc₄Hex₅DeoxyHex₃ glycan profile and MitoQ administration at the acute phase, the levels of HexNAc₄Hex₄ glycan in the subacute phase of MitoQ treatment, and the HexNAc₄Hex₅ glycan profile at the chronic time point phase of MitoQ treatment. These data suggest that these three glycan profiles can be considered molecular signatures for MitoQ-associated neurotherapy. However, further research is required to validate and establish that these three glycan profiles are accurate and sensitive markers associated with TBI neuroprotection.

Spinal cord injury (SCI) remains a major unsolved problem that permanently impairs the lives of innumerable individuals worldwide. Although advances in the basic, pre-clinical and clinical sciences of SCI hold promise for patients, clinicians may lack a full insight into the relevant cellular and molecular events, and laboratory researchers may underappreciate how cellular and molecular phenomena translate into meaningful functional outcomes. To help bridge these perspectives, we first review the American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade, which is the principal instrument used to gauge clinical outcomes in SCI, and the clinically important concept of AIS grade "conversion" (improvement), which occurs in some but not all patients. We then review underlying mechanisms that contribute to the AIS grade and its conversion, including mechanisms of transient neurological dysfunction (neuronal and axonal "stunning"), mechanisms of secondary cell loss (apoptosis, pyroptosis, and necroptosis), and mechanisms of axonal loss (primary axotomy and secondary axonal degeneration). Finally, we briefly review approaches to clinical management that may ameliorate identified mechanisms of secondary tissue loss and neurological dysfunction following SCI.

Patients living with traumatic spinal cord injury (TSCI) have seen many improvements in care and treatment, but life expectancy still falls below the general population. Measuring long-term survival rates and characterizing causes of death are required to identify ways of improving well-being and reduce premature mortality. The study conducted a retrospective analysis of population-based administrative and clinical data from 2001 to 2021 to measure long-term survival of TSCI, mortality predictors, and cause of death. Population-based hospital records linked with administrative databases in British Columbia, Canada, were used to identify those with TSCIs. Demographic and clinical summary statistics were calculated. Mortality rates for 1-, 5-, 10-, 15-, and >15-year survival were calculated using Kaplan-Meier methods. Factors associated with mortality throughout the study period were identified with Cox models. During the study period, 3624 patients were identified with TSCI. The mean age was 51.1 years (SD 21.19) and 2718 (75.0%) were male. Mortality rates at 1, 5, 10, 15, and >15 years were 11.2%, 19.6%, 25.4%, 28.3%, and 29.1%, respectively. Factors associated with mortality included cervical spine injuries, more comorbidities, older age, lower household income, presence of traumatic brain injury, and greater severity of initial injury (p < 0.001). Cardiac disease (22.3%) was the most common cause of death in TSCI patients followed by respiratory diseases (10.2%) and neoplasms (8.5%). The long-term survival of TSCI patients is a significant concern, and preventative measures to avoid injury are critical. Among those suffering TSCI, particularly high death rates are observed in those with cervical injuries, multiple comorbidities, and advanced age. Interventions are needed to reduce premature death among TSCI patients compared with the population.

A traumatic cervical spinal cord injury (cSCI) is a severe consequence of trauma to the cervical spine with high mortality and morbidity rates. Epidemiological studies of traumatic cSCIs are necessary for planning preventive measures and health care resource allocation. This is a retrospective database study of 387 consecutive patients with traumatic cSCI admitted to hospitals in Southeast Norway between 2015 and 2022. The estimated incidence of traumatic cSCI was 1.6 per 100,000 per year. The incidence rates adjusted for standard European and global populations were 1.7 and 1.1 per 100,000 per year, respectively. The median patient age was 64 years, 75% were males, 40% had severe comorbidities, 65% of injuries were caused by falls, 25% were ethanol influenced, 44% had multiple traumas, and 96% were admitted to the Neurotrauma Center (NTC). In patients with C0-C2 injury, an odontoid fracture with dislocation of the odontoid fragment was most frequent. The most frequent subaxial injuries were, according to the AO Spine subaxial cervical spine injury classification system, minor nonstructural injuries (type A0) and translational injuries (type C). Eleven percent of patients were diagnosed with cSCIs at C0-C2, and 89% of cSCIs were subaxial. According to the American Spinal Injury Association (ASIA) Impairment Scale (AIS), 17% of cSCIs were classified as A, 12% B, 24% C, and 47% D. Forty-three percent of patients were classified as central cord syndrome, which was significantly associated with subaxial injuries and preinjury degenerative cervical spinal stenosis. Compromised respiration due to the cSCI itself was diagnosed in 17% of patients and was predominant in patients with complete cSCIs (AIS A or B) and high cervical injuries. These data will be helpful in planning the capacity of NTCs in the future. Interventions to prevent falls in elderly individuals and to increase awareness of ethanol as a risk factor for severe cSCIs are needed.

A meta-analysis of deep vein thrombosis (DVT) in patients with spinal cord injury (SCI) was performed using five databases (PubMed, Embase, the Cochrane Library, Web of Science, and Scopus) from 2000 to March 2023. Observational descriptive studies investigating the prevalence of DVT among patients with SCI were included. Data were retrieved by author, country, continent, gender, age, sample source, and additional variables. Risk of bias was evaluated using the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence. Data and random-effects models were used to synthesize existing findings. Among 45 studies, the overall pooled estimated prevalence of DVT was 14.53% (95% confidence interval [CI], 11.22 - 17.84%) in patients with SCI (n = 87,294), including 14.77% (95% CI, 11.19 - 18.35%) in patients with acute SCI and 19.02% (95% CI, 11.51 - 26.53%) in patients with SCI older than 18 years. A total of 26 studies from hospitals showed that the combined prevalence estimate of DVT in patients with SCI was 16.41% (95% CI, 11.36 - 21.45%), and in 19 studies from rehabilitation institutions was 12.33% (95% CI, 8.25 - 16.42%). Moreover, the prevalence of DVT in patients with SCI is influenced by factors such as regional distribution, demographic characteristics, the extent of nerve damage, the level of the lesion, and the implementation of thromboprophylaxis. We estimated the overall pooled prevalence of DVT after SCI in distinctive characteristics. These findings can provide a reference for future epidemiological studies of DVT in patients with SCI. Given the substantial variety of the included studies (e.g., diagnostic methodologies, demographic characteristics), our results should be interpreted with caution.

Sleep disturbances are among the most prevalent and persistent consequences of traumatic brain injury (TBI), yet they remain underutilized as clinical indicators of injury status. In this perspective, we propose that sleep fragmentation-defined as the frequency of transitions between sleep and wakefulness-represents a functional, scalable, and underrecognized diagnostic biomarker of TBI. Drawing on empirical findings from a mouse model of diffuse TBI, we show that summary measures of sleep fragmentation and duration can reliably distinguish injured from uninjured animals using dimensionality reduction and machine learning techniques. Current biomarkers such as glial fibrillary acidic protein and neurofilament light chain provide valuable insights into structural damage but offer limited information about how injury affects behavior and day-to-day function. Sleep-based metrics, by contrast, reflect neural network integrity and capture ongoing physiological disruption. Critically, these metrics can be collected non-invasively, longitudinally, and in real-world settings using actigraphy, making them a practical complement to blood-based diagnostics that require biological sampling and specialized laboratory infrastructure. Our analysis demonstrates that sleep metrics collected over 48 h post-injury-specifically the number of sleep-wake transitions-carry a strong diagnostic signal. Sleep metrics offer a behaviorally grounded complement aligned with the goals of precision medicine and functional assessment. With further validation, these features may also support monitoring recovery or stratifying injury severity. This perspective highlights sleep fragmentation as a non-invasive diagnostic biomarker for TBI with the potential to enhance individualized monitoring and support early detection efforts in both research and clinical settings.

In acute human spinal cord injury (SCI), magnetic resonance imaging (MRI) reveals progressive neuroanatomical changes at the lesion site and in remote regions. Here, we aimed to elucidate the structural underpinnings of these neuroanatomical changes and to characterize their spatiotemporal distribution in a rat contusion SCI model, using both histology and MRI. First, rats subjected to a thoracic contusion SCI (T8) and sham-operated rats were sacrificed at 56 days post-injury (dpi), and SMI-32 immunohistochemistry was used to assess remote axonal degeneration at cervical segments C2-C5. Second, to evaluate the effect of severity and time since injury on axonal degeneration, rats of varying injury severity were sacrificed at 2, 30, and 90 dpi, respectively, followed by SMI-32 immunohistochemistry. Third, ex vivo structural MRI and diffusion tensor imaging were performed rostral to the injury site (C3-T6) at 90 dpi. Histological evidence of axonal degeneration emerged as early as 2 dpi rostral to the injury site, persisting at 90 dpi. Severity-dependent degeneration occurred within the fasciculus gracilis and the periphery of the medio- and ventrolateral columns. Corresponding MRI changes, including lower fractional anisotropy in these regions and smaller gray matter area, were detected. In contrast, the dorsal corticospinal tract exhibited lower fractional anisotropy without clear histological abnormalities, potentially due to atrophy-related mislocalization. This highlights the value of correlative, multimodal approaches and the need for further methodological refinement. The number of SMI-32+ axonal profiles correlated negatively, while gray matter area and fractional anisotropy correlated positively with locomotion assessed by Basso, Beattie, and Bresnahan scores. This study demonstrates in independent experiments that neuroanatomical MRI changes observed after SCI, occurring remote from the injury site, are linked to axonal degeneration. Experimental SCI offers translational insights into underlying mechanisms and potential avenues for neuroprotective or rehabilitative approaches.