Early recovery of walking in children and youths after traumatic brain injury

A consecutive series of 106 children and adolescents (mean age 10 years, 6 months; SD 4 years, 8 months) with recent traumatic brain injury admitted to a regional hospital-based rehabilitation program was assessed to determine the rate of walking recovery, and characteristics that distinguish between independent walkers, non-walkers, and device-assisted walkers at hospital discharge. Data were collected through a retrospective medical record review of patients admitted between 1994 and 2001. Mean hospital stays were 66.7 days (SD 88.5, range 7 to 140 days). All children (72 male, 34 female) had recent injuries (from 1 to 8 weeks after onset of traumatic brain injury) and were independent walkers before injury. Sixty-four children (60.4%) were discharged as independent walkers, 13 (12.3%) walked with the assistance of a device, and 29 (27.3%) were non-walkers. Non-walkers had a higher proportion of prolonged loss of consciousness, lower-extremity injury, impaired responsiveness, and lower-extremity spasticity than independent walkers. In addition, non-walkers had poorer discharge mobility and social function scores, longer average hospital stays, and a greater proportion of non-community discharges. Device-only walkers were older, more likely to be male, and had a higher proportion of lower-extremity injuries than independent walkers. Results highlight several demographic, clinical, and outcome variables that distinguish independent walkers from device-assisted walkers and non-walkers. These variables might help to determine the prognosis for ambulation, resource needs, and discharge plans for children and adolescents with traumatic brain injury after episodes of inpatient rehabilitation.

To investigate the impact of traumatic injury on the developing prefrontal-temporal adolescent cortex, and correlated brain structural measures with neurocognitive functioning. Nineteen adolescents (12 males, 7 females, age range: 11-17y, mean 15y 8mo, standard deviation 1y 7mo, median 15y 11mo) with traumatic brain injury (TBI) were included. Cortical thickness of frontal and temporal lobes was assessed using magnetic resonance imaging. We correlated cortical thickness of prefrontal-temporal regions with age, time since injury, and neurocognitive functioning, and compared these results with a matched control cohort without TBI. We found thinner prefrontal (p=0.039) and temporal cortices (p=0.002) in adolescents with TBI compared to typically developing children. Furthermore, significant age effect was observed on the prefrontal (r=-0.75, p=0.003) and temporal (r=-0.66, p=0.013) cortical thickness in typically developing adolescents, but not in adolescents with TBI. Executive function (measured using the Behaviour Rating Inventory of Executive Function questionnaire, with lower scores meaning higher functioning) was correlated with prefrontal cortical thickness in typically developing adolescents (r=0.72, p=0.009). Opposite trends were found for correlations between cortical thickness and executive function in the TBI and control cohort. Structural maturation in typically developing adolescents correlates with functional development: the older the adolescent, the thinner the prefrontal cortex, the better executive function. In adolescents with TBI we observed an opposite trend, that appeared significantly different from the control group: the thinner the prefrontal and temporal cortex, the worse executive functioning. Cortical thickness is negatively correlated with age in typically developing adolescents. Prefrontal cortex thickness correlates negatively with executive function in typically developing adolescents. Correlations between cortical thickness and executive functioning rise for adolescents without traumatic brain injury (TBI). Correlations between cortical thickness and executive functioning fall for adolescents with TBI. Adolescents with TBI have a long-term impairment of adaptive functioning in daily living.

Oxidative stress is a pivotal mechanism implicated in the onset of traumatic brain injury (TBI), yet its precise role remains elusive. This study aims to elucidate the potential molecular interactions between key genes associated with oxidative stress and their influence on TBI pathogenesis. TBI dataset and oxidative stress-related genes sourced from Public databases. Differential expression analysis and machine learning models were executed to select key genes, which were further validated using receiver operating characteristic (ROC) curves. A nomogram was constructed for diagnostic prediction, and enrichment analysis explored pathways associated with key genes. Immune infiltration analysis and regulatory network construction were conducted. Molecular validation included RT-qPCR and Western blotting using rat brain tissue to assess gene and protein expression levels. In our study, we identified 400 differentially expressed genes (DEGs) between TBI and normal samples, including 20 oxidative stress-related genes. Machine learning analysis highlighted AKR1C2, QDPR, CYP3A5, CNTF, and PNPT1 as key genes with diagnostic potential (AUC > 0.6). Functional analysis revealed significant involvement of these genes in immune processes and metabolic regulation. Further, immune cell infiltration analysis showed notable differences in effector memory CD8 T cells. Molecular validation through RT-qPCR and Western blot confirmed the overexpression of key genes PNPT1 and QDPR in TBI models, substantiating their potential role in TBI pathology. Our study revealed the potential mechanisms of action for PNPT1 and QDPR in TBI, offering valuable insights into their roles in TBI pathology. These findings opened new avenues for future therapeutic strategies in TBI treatment.

Defense and Veterans Brain Injury Center: The First 25 Years

Gender as a Moderator of Cognitive and Affective Outcome After Traumatic Brain Injury

This study examined the association that chronic pain (CP) has with suicidal ideation (SI) and suicide attempt (SA) among individuals with moderate-to-severe traumatic brain injury (TBI). Participants who completed inpatient rehabilitation at a TBI Model Systems (TBIMS) center. In total, 2579 English-speaking participants within 10years of moderate-to-severe TBI who completed the CP Survey at TBIMS follow-up. A multisite, cross-sectional observational cohort study. Suicidal ideation and SA; experience with CP; demographic variables, injury characteristics, behavioral health, and functional characteristics. At follow-up assessment, 45.2% endorsed current CP, 14.5% reported a history of CP after TBI that had resolved, and 40.3% reported no CP since the onset of TBI. There were significant differences in prevalence of SI (P < .001) and SA (P=.018) among the pain groups, with the highest prevalence observed within the current CP group (14.8% and 2.6%, respectively). Adjusting for other covariates, multivariate logistic regression models indicated a significantly higher likelihood of SI for the current CP versus no CP group (OR=2.05, 95% CI=1.38, 3.06). No significant association was found between the pain groups and SA. Clinical elevated symptoms of posttraumatic stress at follow-up were associated with both SI (OR=3.87, 95% CI=2.76, 5.44) and SA (OR=2.43; 95% CI=1.25, 4.75). Those with TBI caused by violence or falls had a lower risk of SI compared to those with a vehicular-related cause of TBI. Increased SI risk was also associated with lower functional independence and participation in preinjury mental health services; risk of SA was associated with Hispanic ethnicity. The current study supports further investigation on how CP and its specific attributes may influence suicide-related outcomes. These findings warrant consideration of strategies to proactively assess suicide risk and the potential development of interventions targeting suicidal behavior among individuals experiencing both CP and TBI.

This paper explores the effects of hydroxysafflor yellow A (HSYA) on traumatic brain injury (TBI). Rats were divided into four groups: control, TBI, TBI combined with HSYA, and TBI combined with nimodipine. Saline, HSYA, or nimodipine was i.v. injected at 30 min before and 6 h after the onset of TBI. The contusion volume of brain, mitochondrial ATPase activity, brain malondialdehyde (MDA) content, and the concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in the blood plasma were investigated. The results showed that the inhibitory rate of HSYA at a dose of 4 mg/kg was 59.2% compared with the TBI group. After the insult by TBI for 48 h, the activity of Na+, K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase decreased to 31, 35, and 38% of control group. HSYA increased these ATPase activities by 162, 96, and 131% of TBI group. HSYA also increased superoxide dismutase activity and decreased MDA content in the right parietal lobe adjacent to contusion foci in TBI rats. HSYA enhanced the t-PA activity by 64.64%, decreased the PAI-1 activity by 71.88%, and decreased the MMP-9 expression to 49.11% in the hippocampus of the TBI group at 12 h. In conclusion, HSYA may exert a potential therapeutic strategy to improve the outcome following TBI injury.

Objective To investigate the neuroprotective effect of dexmedetomidine in traumatic brain injury (TBI) rat model and the relationship with clearance of oxygen free radicals and the erythroid-derived nuclear factor-related factor 2 (Nrf2)-antioxidant/electrophilic response element (ARE) signal pathway. Methods Healthy adult male SD rats weighing 300-350 g were selected to construct a TBI model. Sixty rats were divided into three groups: sham operation group (Sham group), traumatic brain injury group (TBI group) and dexmedetomidine (TBI+ DEX group) group. In Sham group, only brain skulls were removed. In TBI and TBI+ DEX groups, the rats were all prepared with a modified free-fall device to induce traumatic brain injury . Rats in TBI and TBI+ DEX groups received same amount of saline and dexmedetomidine (100 μg/kg) treatment 1 h after the onset of TBI respectively. Neurological function was evaluated by modified neurological deficit scores (mNss), and cerebral edema was evaluated by brain dry-wet weight method. The enzyme activity kit was used to detect the antioxidant enzymes SOD and MDA after 24 hours of injury. Finally, Western blot, RT-qPCR and immunofluorescence methods were used to detect the expression level of Nrf2-ARE signaling pathway and its downstream molecules HO-1, NQO-1expression. Results Compared with TBI group, mNss scores in DEX group were significantly lower (P<0.05). DEX could significantly reduce brain edema (P<0.05); DEX could significantly reduce the levels of antioxidant enzyme SOD and oxidative stress product MDA (P<0.05). Conclusion DEX can activate Nrf2-ARE signaling pathway to induce the expression of target genes such as antioxidant/detoxifying enzymes downstream to inhibit oxidative stress and exert neuroprotection. Key words: Dexmedetomidine; Nrf2-ARE signal pathway; Traumatic brain injury; Oxidative stress

Traumatic brain injury is a major cause of death and disability worldwide, affecting over 69 million individuals yearly. One-carbon metabolism has been shown to have beneficial effects after brain damage, such as ischemic stroke. However, whether increasing one-carbon metabolite vitamins impacts traumatic brain injury outcomes in patients requires more investigation. The aim of this review is to evaluate how one-carbon metabolites impact outcomes after the onset of traumatic brain injury. PubMed, Web of Science, and Google Scholar databases were searched for studies that examined the impact of B-vitamin supplementation on traumatic brain injury outcomes. The search terms included combinations of the following words: traumatic brain injury, dietary supplementation, one-carbon metabolism, and B-vitamins. The focus of each literature search was basic science data. The year of publication in the literature searches was not limited. Our analysis of the literature has shown that dietary supplementation of B-vitamins has significantly improved the functional and behavioral recovery of animals with traumatic brain injury compared to controls. However, this improvement is dosage-dependent and is contingent upon the onset of supplementation and whether there is a sustained or continuous delivery of vitamin supplementation post-traumatic brain injury. The details of supplementation post-traumatic brain injury need to be further investigated. Overall, we conclude that B-vitamin supplementation improves behavioral outcomes and reduces cognitive impairment post-traumatic brain injury in animal model systems. Further investigation in a clinical setting should be strongly considered in conjunction with current medical treatments for traumatic brain injury-affected individuals.

Risk of pre-existing hyponatremia and mortality in patients with traumatic brain injury across age groups

To examine the self-reported prevalence of long-term health issues in individuals with traumatic brain injury (TBI) living in the community. A structured health interview. For individuals with TBI, the presence of a specific health-related issue with onset post-TBI and currently a problem at the time of the interview was explored. For individuals without disability, a specific health-related issue was evaluated at time of interview. For each health issue, the proportion of individuals with TBI experiencing post-TBI onset but current symptoms was contrasted with symptom reports of individuals without disability. Chi-square statistical analyses were used to determine significance. For individuals with TBI, logistic regressions were used to model the probability of having a particular health difficulty when four covariates were examined, such as age, gender, time since onset of TBI, and duration of loss of consciousness (LOC). Urban, suburban, and rural New York State. 338 individuals with TBI and 273 individuals without disability between the ages of 18 and 65 years. Individuals with TBI were, on average, 10 years post-onset at the time of interview. Self-reported health issues reflective of neuroendocrine, neurological, immunosuppression, and other health issues. Chronic health issues suggestive of ongoing neuroendocrine dysfunctions (ie, changes in hair/skin texture, body temperature changes), neurologic difficulties (ie, headaches, seizures, balance difficulties, spasticity, sleep disturbances, loss of urinary control), and arthritic complaints were significantly more common in individuals with TBI. The prevalence of many of these health-related difficulties was related to duration of LOC but not to time since injury. Age and gender effects were found, with older women with TBI more likely to report thyroid conditions, sleep disturbances, loss of urinary control, and arthritic changes. Women also reported greater frequency of headaches, colds, weight changes, and temperature changes post TBI. Health issues reflective of neuroendocrine, neurological, and arthritic difficulties are common long-term health issues for individuals with TBI. Proactive patient education, ongoing health screening with appropriate medical follow-up, and timely interventions for individuals with TBI are indicated. Longitudinal studies are necessary to examine the natural course of post-TBI health difficulties.

Traumatic axonal injury of the medial lemniscus pathway in a patient with traumatic brain injury: validation by diffusion tensor tractography.

Traumatic brain injury (TBI) is a major cause of death and disability. Despite its importance in public health, there are presently no drugs to treat TBI. Many reasons underlie why drugs have failed clinical trials, one reason is that most drugs to treat TBI lose much of their efficacy before patients are first treated. This review discusses the importance of therapeutic time window; the time interval between TBI onset and the initiation of treatment. Therapeutic time window is complex, as brain injury is both acute and chronic, resulting in multiple drug targets that appear and disappear with differing kinetics. The speed and increasing complexity of TBI pathophysiology is a major reason why drugs lose efficacy as time to first dose increases. Recent Phase III clinical trials treated moderate to severe TBI patients within 4–8 h after injury, yet they turned away many potential patients who could not be treated within these time windows. Additionally, most head trauma is mild TBI. Unlike moderate to severe TBI, patients with mild TBI often delay treatment until their symptoms do not abate. Thus, drugs to treat moderate to severe TBI likely will need to retain high efficacy for up to 12 h after injury; drugs for mild TBI, however, will likely need even longer windows. Early pathological events following TBI progress with similar kinetics in humans and animal TBI models suggesting that preclinical testing of time windows assists the design of clinical trials. We reviewed preclinical studies of drugs first dosed later than 4 h after injury. This review showed that therapeutic time window can differ depending upon the animal TBI model and the outcome measure. We identify the few drugs (methamphetamine, melanocortin, minocycline plus N-acetylcysteine, and cycloserine) that demonstrated good therapeutic windows with multiple outcome measures. On the basis of their therapeutic window, these drugs appear to be excellent candidates for clinical trials. In addition to further testing of these drugs, we recommend that the assessment of therapeutic time window with multiple outcome measures becomes a standard component of preclinical drug testing.

To investigate associations of lifetime history of traumatic brain injury (TBI) with prescription opioid use and misuse among noninstitutionalized adults. Ohio Behavioral Risk Factor Surveillance System (BRFSS) participants in the 2018 cohort who completed the prescription opioid and lifetime history of TBI modules (n = 3448). Secondary analyses of a statewide population-based cross-sectional survey. Self-report of a lifetime history of TBI using an adaptation of the Ohio State University TBI-Identification Method. Self-report of past year: (1) prescription pain medication use (ie, prescription opioid use); and (2) prescription opioid misuse, defined as using opioids more frequently or in higher doses than prescribed and/or using a prescription opioid not prescribed to the respondent. In total, 22.8% of adults in the sample screened positive for a lifetime history of TBI. A quarter (25.5%) reported past year prescription opioid use, and 3.1% met criteria for prescription opioid misuse. A lifetime history of TBI was associated with increased odds of both past year prescription opioid use (adjusted odds ratio [AOR] = 1.52; 95% CI, 1.27-1.83; P < .01) and prescription opioid misuse (AOR = 1.65; 95% CI, 1.08-2.52; P < .05), controlling for sex, age, race/ethnicity, and marital status. Results from this study support the "perfect storm" hypothesis-that persons with a history of TBI are at an increased risk for exposure to prescription opioids and advancing to prescription opioid misuse compared with those without a history of TBI. Routine screening for a lifetime history of TBI may help target efforts to prevent opioid misuse among adults.

Hyperbaric oxygen effects on neuronal apoptosis associations in a traumatic brain injury rat model