Xuefu Zhuyu decoction promotes synaptic plasticity by targeting miR-191a-5p/BDNF-TrkB axis in severe traumatic brain injury.

BACKGROUND: Xuefu Zhuyu decoction (XFZYD) is a traditional Chinese herbal formula known for its ability to eliminate blood stasis and improve blood circulation, providing neuroprotection against severe traumatic brain injury (sTBI). However, the underlying mechanism is still unclear. PURPOSE: We aim to investigate the neuroprotective effects of XFZYD in sTBI from a novel mechanistic perspective of miRNA-mRNA. Additionally, we sought to elucidate a potential specific mechanism by integrating transcriptomics, bioinformatics, and conducting both in vitro and in vivo experiments. METHODS: The sTBI rat model was established, and the rats were treated with XFZYD for 14 days. The neuroprotective effects of XFZYD were evaluated using a modified neurological severity score, hematoxylin and eosin staining, as well as Nissl staining. The anti-inflammatory effects of XFZYD were explored using quantitative real-time PCR (qRT-PCR), Western blot analysis, and immunofluorescence. Next, miRNA sequencing of the hippocampus was performed to determine which miRNAs were differentially expressed. Subsequently, qRT-PCR was used to validate the differentially expressed miRNAs. Target core mRNAs were determined using various methods, including miRNA prediction targets, mRNA sequencing, miRNA-mRNA network, and protein-protein interaction (PPI) analysis. The miRNA/mRNA regulatory axis were verified through qRT-PCR or Western blot analysis. Finally, morphological changes in the neural synapses were observed using transmission electron microscopy and immunofluorescence. RESULTS: XFZYD exhibited significant neuroprotective and anti-inflammatory effects on subacute sTBI rats' hippocampus. The analyses of miRNA/mRNA sequences combined with the PPI network revealed that the therapeutic effects of XFZYD on sTBI were associated with the regulation of the rno-miR-191a-5p/BDNF axis. Subsequently, qRT-PCR and Western blot analysis confirmed XFZYD reversed the decrease of BDNF and TrkB in the hippocampus caused by sTBI. Additionally, XFZYD treatment potentially increased the number of synaptic connections, and the expression of the synapse-related protein PSD95, axon-related protein GAP43 and neuron-specific protein TUBB3. CONCLUSIONS: XFZYD exerts neuroprotective effects by promoting hippocampal synaptic remodeling and improving cognition during the subacute phase of sTBI through downregulating of rno-miR-191a-5p/BDNF axis, further activating BDNF-TrkB signaling.

Computer-Assisted Rehabilitation Shows Greater Efficacy Than Traditional in Visuospatial Skills and Cognition in Neglect Patients.

This study is crucial for improving unilateral spatial neglect (USN) treatments, focusing on comparing the effectiveness of computer-assisted cognitive rehabilitation (CACR) against conventional rehabilitation (CR) methods. It aimed to address a significant research gap and improve patient outcomes by evaluating the impact of CACR versus CR on visuospatial perception, visual field and attention, and visual memory in patients with USN. This study was a randomized controlled trial. Forty-five consecutive patients with USN from a university rehabilitation center were divided into two groups: 22 patients received CACR with Rehacom software, focusing on saccadic eye movement, visual field, and visual-motor coordination, while 23 underwent CR that combined hemispheric activation approach, mental imagery training, and vibration therapy. Assessments included the Motor-Free Visual Perception Test (MVPT), Line Bisection Test (LBT), Visual Span Test (VST), and Visual Recognition Test (VRT). The study employed ANCOVA and effect size calculations to evaluate the effectiveness of CACR compared to CR in treating patients with USN. Results indicated that CACR significantly outperformed CR in improving visuospatial perception, visual field, attention, and memory, showcasing its effectiveness in treating USN. These findings demonstrate the superiority of CACR over CR, particularly in enhancing visual memory and attention, as evidenced by the large effect size in VRT and moderate effects in LBT and VST. This suggests CACR's potential as a more effective approach for rehabilitation in patients with USN due to brain injuries.

Effectiveness of biomedical interventions on the chronic stage of traumatic brain injury: a systematic review of randomized controlled trials.

Traumatic brain injury (TBI), in any form and severity, can pose risks for developing chronic symptoms that can profoundly hinder patients' work/academic, social, and personal lives. In the past 3 decades, a multitude of pharmacological, stimulation, and exercise-based interventions have been proposed to ameliorate symptoms, memory impairment, mental fatigue, and/or sleep disturbances. However, most research is preliminary, thus limited influence on clinical practice. This review aims to systematically appraise the evidence derived from randomized controlled trials (RCT) regarding the effectiveness of pharmacological, stimulation, and exercise-based interventions in treating chronic symptoms due to TBI. Our search results indicate that despite the largest volume of literature, pharmacological interventions, especially using neurostimulant medications to treat physical, cognitive, and mental fatigue, as well as daytime sleepiness, have yielded inconsistent results, such that some studies found improvements in fatigue (e.g., Modafinil, Armodafinil) while others failed to yield the improvements after the intervention. Conversely, brain stimulation techniques (e.g., transcranial magnetic stimulation, blue light therapy) and exercise interventions were effective in ameliorating mental health symptoms and cognition. However, given that most RCTs are equipped with small sample sizes, more high-quality, larger-scale RCTs is needed.

Sex-specific antioxidant biomarker depletion in patients with a history of mild traumatic brain injury.

Individuals with a history of mild traumatic brain injury (mTBI) are at an increased risk for neurodegenerative disease, suggesting that intrinsic neuroprotective mechanisms, such as the endogenous antioxidant reservoir, may be depleted long-term after mTBI. Here, we retrospectively analyzed symptoms and blood antioxidants in patients with a history of mTBI who presented to Resilience Code, a sports medicine clinic in Colorado. Significant decreases in alpha-tocopherol, selenium, linoleic acid, taurine, docosahexaenoic acid, and total omega-3 were measured in the total mTBI population versus controls. Male mTBI patients showed depletion of a larger array of antioxidants than females. Patients with a history of mTBI also reported significantly worsened emotional, energy, head, and cognitive symptoms, with males displaying more extensive symptomology. Multiple or chronic mTBI patients had worsened symptoms than single or acute/subchronic mTBI patients, respectively. Finally, male mTBI patients with the largest reductions in polyunsaturated fatty acids (PUFAs) displayed worse symptomology than male mTBI patients with less depletion of this antioxidant reservoir. These results demonstrate that antioxidant depletion persists in patients with a history of mTBI and these deficits are sex-specific and associated with worsened symptomology. Furthermore, supplementation with specific antioxidants, like PUFAs, may diminish symptom severity in patients suffering from chronic effects of mTBI.

[Role of NLRP3 inflammasome in prevention and treatment of cognitive impairment-related diseases and traditional Chinese medicine intervention: a review].

Alzheimer's disease(AD), vascular dementia(VD), and traumatic brain injury(TBI) are more common cognitive impairment diseases characterized by high disability and mortality rates, imposing a heavy burden on individuals and their families. Although AD, VD, and TBI have different specific mechanisms, their pathogenesis is closely related to the nucleotide-binding oligome-rization domain-like receptor protein 3(NLRP3). The NLRP3 inflammasome is involved in neuroinflammatory responses, mediating microglial polarization, regulating the reduction of amyloid ß-protein(Aß) deposition, neurofibrillary tangles(NFTs) formation, autophagy regulation, and maintaining brain homeostasis, and synaptic stability, thereby contributing to the development of AD, VD, and TBI. Previous studies have shown that traditional Chinese medicine(TCM) can alleviate neuroinflammation, promote microglial polarization towards the M2 phenotype, reduce Aß deposition and NFTs formation, regulate autophagy, and maintain brain homeostasis by intervening in NLRP3 inflammasome, hence exerting a role in preventing and treating cognitive impairment-related diseases, reducing psychological and economic pressure on patients, and improving their quality of life. Therefore, this article elucidated the role of NLRP3 inflammasome in AD, VS, and TBI, and provided a detailed summary of the latest research results on TCM intervention in NLRP3 inflammasome for the prevention and treatment of these diseases, aiming to inherit the essence of TCM and provide references and foundations for clinical prevention and treatment of cognitive impairment-related diseases with TCM. Meanwhile, this also offers insights and directions for further research in TCM for the prevention and treatment of cognitive impairment-related diseases.

Allocating municipal services to individuals with complex rehabilitation needs - a discourse analysis of individual administrative decision letters.

BACKGROUND: Rehabilitation is considered paramount for enhancing quality of life and reducing healthcare costs. As a result of healthcare reforms, Norwegian municipalities have been given greater responsibility for allocating rehabilitation services following discharge from hospital. Individual decision letters serve as the basis for implementing services and they have been described as information labels on the services provided by the municipality. They play an important role in planning and implementing the services in collaboration with the individual applicants. Research indicates that the implementation of policies may lead to unintended consequences, as individuals receiving municipal services perceive them as fragmented. This perception is characterised by limited user involvement and a high focus on body functions. The aim of this study was to examine how municipal decision letters about service allocation incorporate the recommendations made in the official national guideline and reflect a holistic approach to rehabilitation, coordination and user involvement for individuals with comprehensive needs. METHODS: The decision letters of ten individuals with moderate to severe brain injury allocating rehabilitation services in two municipalities were examined. It was assessed whether the content was in accordance with the authorities' recommendations, and a discourse analysis was conducted using four tools adapted from an established integrated approach. RESULTS: The letters primarily contained standard texts concerning legal and administrative regulations. They were predominantly in line with the official guideline to municipal service allocation. From a rehabilitation perspective, the focus was mainly on medically oriented care, scarcely referring to psychosocial needs, activity, and participation. The intended user involvement seemed to vary between active and passive status, while the coordination of services was given limited attention. CONCLUSIONS: The written decision letters did fulfil legal and administrative recommendations for service allocation. However, they did not fulfil their potential to serve as a means of conveying rehabilitation issues, such as specification of the allocated services, a holistic approach to health, coordination, or the involvement of users in decision processes. These elements must be incorporated throughout the allocation process if the policies are to be implemented as intended. Findings can have international relevance for discussions between clinicians and policy makers.

Neutrophil Extracellular Traps Regulate Surgical Brain Injury by Activating the cGAS-STING Pathway.

Surgical brain injury (SBI), induced by neurosurgical procedures or instruments, has not attracted adequate attention. The pathophysiological process of SBI remains sparse compared to that of other central nervous system diseases thus far. Therefore, novel and effective therapies for SBI are urgently needed. In this study, we found that neutrophil extracellular traps (NETs) were present in the circulation and brain tissues of rats after SBI, which promoted neuroinflammation, cerebral edema, neuronal cell death, and aggravated neurological dysfunction. Inhibition of NETs formation by peptidylarginine deiminase (PAD) inhibitor or disruption of NETs with deoxyribonuclease I (DNase I) attenuated SBI-induced damages and improved the recovery of neurological function. We show that SBI triggered the activation of cyclic guanosine monophosphate-adenosine monophosphate synthase stimulator of interferon genes (cGAS-STING), and that inhibition of the cGAS-STING pathway could be beneficial. It is worth noting that DNase I markedly suppressed the activation of cGAS-STING, which was reversed by the cGAS product cyclic guanosine monophosphate-adenosine monophosphate (cGMP-AMP, cGAMP). Furthermore, the neuroprotective effect of DNase I in SBI was also abolished by cGAMP. NETs may participate in the pathophysiological regulation of SBI by acting through the cGAS-STING pathway. We also found that high-dose vitamin C administration could effectively inhibit the formation of NETs post-SBI. Thus, targeting NETs may provide a novel therapeutic strategy for SBI treatment, and high-dose vitamin C intervention may be a promising translational therapy with an excellent safety profile and low cost.

Case Characterization and Perceptions of Athletic Trainers Regarding Medical Disqualification Following Concussion.

CONTEXT: Medical disqualification (MDQ) following concussion is a challenging decision clinicians may encounter with little evidence-based guidance. OBJECTIVE: We aimed to 1) describe the MDQ following concussion cases athletic trainers (ATs) have been involved in, 2) describe beliefs about MDQ following concussion, and 3) explore factors that ATs believed should be involved in the MDQ following concussion process. DESIGN: Mixed methods. SETTING: Online cross-sectional survey with follow-up semi-structured interviews. PARTICIPANTS: ATs (n=502) employed at the collegiate setting completed a survey (completion rate=82.3%, n=413/502; male=175, 34.9%; female=235, 46.8%, prefer not to answer=4, 0.8%; no response=88, 17.5%; age=35.3±10.8 years). Twenty participants were also interviewed (males=13, 65.0%; females=7, 35.0%; average age=40.7±11.0years). DATA COLLECTION AND ANALYSIS: Participants completed a cross-sectional survey comprised of three sections of MDQ experience and specific case information, MDQ beliefs, and demographic items. We also interviewed participants that completed the survey and indicated involvement in at least one MDQ following concussion case. We addressed aims 1 and 2 using descriptive statistics and aim 3 with a five-cycle content analysis. RESULTS: Nearly half of respondents had been involved in an MDQ case following concussion (49.0% n=246; not involved=51.0%, n=256). ATs who had been involved in at least one MDQ case had involvement in an average of 2.3±1.9 cases (n=241). Participants often described many factors they believed should influence the MDQ decision including sport type, concussion history and recovery, health-related quality of life, and academic performance. CONCLUSIONS: Our findings highlight that nearly half of participants were involved in an MDQ case following concussion and navigated this process without guidelines. Given this, multiple factors were considered to evaluate the patient's well-being holistically. The number of ATs involved in MDQ cases following concussion and factors that guided this process warrant further research to develop evidence-based recommendations that assist clinicians in these difficult decisions.

Protective Effects of Plant-Derived Compounds Against Traumatic Brain Injury.

Inflammation in the nervous system is one of the key features of many neurodegenerative diseases. It is increasingly being identified as a critical pathophysiological primitive mechanism associated with chronic neurodegenerative diseases following traumatic brain injury (TBI). Phytochemicals have a wide range of clinical properties due to their antioxidant and anti-inflammatory effects. Currently, there are few drugs available for the treatment of neurodegenerative diseases other than symptomatic relief. Numerous studies have shown that plant-derived compounds, in particular polyphenols, protect against various neurodegenerative diseases and are safe for consumption. Polyphenols exert protective effects on TBI via restoration of nuclear factor kappa B (NF-κB), toll-like receptor-4 (TLR4), and Nod-like receptor family proteins (NLRPs) pathways. In addition, these phytochemicals and their derivatives upregulate the phosphatidylinositol-3-Kinase/Protein Kinase B (PI3K/AKT) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways, which have critical functions in modulating TBI symptoms. There is supporting evidence that medicinal plants and phytochemicals are protective in different TBI models, though future clinical trials are needed to clarify the precise mechanisms and functions of different polyphenolic compounds in TBI.

Head Injury Treatment With Healthy and Advanced Dietary Supplements: A Pilot Randomized Controlled Trial of the Tolerability, Safety, and Efficacy of Branched Chain Amino Acids in the Treatment of Concussion in Adolescents and Young Adults.

Concussion is a common injury in the adolescent and young adult populations. Although branched chain amino acid (BCAA) supplementation has shown improvements in neurocognitive and sleep function in pre-clinical animal models of mild-to-moderate traumatic brain injury (TBI), to date, no studies have been performed evaluating the efficacy of BCAAs in concussed adolescents and young adults. The goal of this pilot trial was to determine the efficacy, tolerability, and safety of varied doses of oral BCAA supplementation in a group of concussed adolescents and young adults. The study was conducted as a pilot, double-blind, randomized controlled trial of participants ages 11-34 presenting with concussion to outpatient clinics (sports medicine and primary care), urgent care, and emergency departments of a tertiary care pediatric children's hospital and an urban tertiary care adult hospital, between June 24, 2014 and December 5, 2020. Participants were randomized to one of five study arms (placebo and 15 g, 30 g, 45 g, and 54 g BCAA treatment daily) and followed for 21 days after enrollment. Outcome measures included daily computerized neurocognitive tests (processing speed, the a priori primary outcome; and attention, visual learning, and working memory), symptom score, physical and cognitive activity, sleep/wake alterations, treatment compliance, and adverse events. In total, 42 participants were randomized, 38 of whom provided analyzable data. We found no difference in our primary outcome of processing speed between the arms; however, there was a significant reduction in total symptom score (decrease of 4.4 points on a 0-54 scale for every 500 g of study drug consumed, p value for trend = 0.0036, [uncorrected]) and return to physical activity (increase of 0.503 points on a 0-5 scale for every 500 g of study drug consumed, p value for trend = 0.005 [uncorrected]). There were no serious adverse events. Eight of 38 participants reported a mild (not interfering with daily activity) or moderate (limitation of daily activity) adverse event; there were no differences in adverse events by arm, with only two reported mild adverse events (both gastrointestinal) in the highest (45 g and 54 g) BCAA arms. Although limited by slow enrollment, small sample size, and missing data, this study provides the first demonstration of efficacy, as well as safety and tolerability, of BCAAs in concussed adolescents and young adults; specifically, a dose-response effect in reducing concussion symptoms and a return to baseline physical activity in those treated with higher total doses of BCAAs. These findings provide important preliminary data to inform a larger trial of BCAA therapy to expedite concussion recovery.

Rhodiola crenulata alleviates hypobaric hypoxia-induced brain injury by maintaining BBB integrity and balancing energy metabolism dysfunction.

BACKGROUND/PURPOSE: Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba (R. crenulate), a famous and characteristic Tibetan medicine, has been demonstrated to exert an outstanding brain protection role in the treatment of high-altitude hypoxia disease. However, the metabolic effects of R. crenulate on high-altitude hypoxic brain injury (HHBI) are still incompletely understood. Herein, the anti-hypoxic effect and associated mechanisms of R. crenulate were explored through both in vivo and in vitro experiments. STUDY DESIGN/METHODS: The mice model of HHBI was established using an animal hypobaric and hypoxic chamber. R. crenulate extract (RCE, 0.5, 1.0 and 2.0 g/kg) and salidroside (Sal, 25, 50 and 100 mg/kg) was given by gavage for 7 days. Pathological changes and neuronal apoptosis of mice hippocampus and cortex were evaluated using H&E and TUNEL staining, respectively. The effects of RCE and Sal on the permeability of blood brain barrier (BBB) were detected by Evans blue staining and NIR-II fluorescence imaging. Meanwhile, the ultrastructural BBB and cerebrovascular damages were observed using a transmission electron microscope (TEM). The levels of tight junction proteins Claudin-1, ZO-1 and occludin were detected by immunofluorescence. Additionally, the metabolites in mice serum and brain were determined using UHPLC-MS and MALDI-MSI analysis. The cell viability of Sal on hypoxic HT22 cells induced by CoCl2 was investigated by cell counting kit-8. The contents of LDH, MDA, SOD, GSH-PX and SDH were detected by using commercial biochemical kits. Meanwhile, intracellular ROS, Ca2+ and mitochondrial membrane potential were determined by corresponding specific labeled probes. The intracellular metabolites of HT22 cells were performed by the targeted metabolomics analysis of the Q300 kit. The cell apoptosis and necrosis were examined by YO-PRO-1/PI, Annexin V/PI and TUNEL staining. In addition, mitochondrial morphology was tested by Mito-tracker red with confocal microscopy and TEM. Real-time ATP production, oxygen consumption rate, and proton efflux rate were measured using a Seahorse analyzer. Subsequently, MCU, OPA1, p-Drp1ser616, p-AMPKα, p-AMPKß and Sirt1 were determined by immunofluorescent and western blot analyses. RESULTS: The results demonstrated that R. crenulate and Sal exert anti-hypoxic brain protection from inhibiting neuronal apoptosis, maintaining BBB integrity, increasing tight junction protein Claudin-1, ZO-1 and occludin and improving mitochondrial morphology and function. Mechanistically, R. crenulate and Sal alleviated HHBI by enhancing the tricarboxylic acid cycle to meet the demand of energy of brain. Additionally, experiments in vitro confirmed that Sal could ameliorate the apoptosis of HT22 cells, improve mitochondrial morphology and energy metabolism by enhancing mitochondrial respiration and glycolysis. Meanwhile, Sal-mediated MCU inhibited the activation of Drp1 and enhanced the expression of OPA1 to maintain mitochondrial homeostasis, as well as activation of AMPK and Sirt1 to enhance ATP production. CONCLUSION: Collectively, the findings suggested that RCE and Sal may afford a protective intervention in HHBI through maintaining BBB integrity and improving energy metabolism via balancing MCU-mediated mitochondrial homeostasis by activating the AMPK/Sirt1 signaling pathway.

Computational Fractal-Based Analysis of MR Susceptibility-Weighted Imaging (SWI) in Neuro-Oncology and Neurotraumatology.

Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) technique able to depict the magnetic susceptibility produced by different substances, such as deoxyhemoglobin, calcium, and iron. The main application of SWI in clinical neuroimaging is detecting microbleedings and venous vasculature. Quantitative analyses of SWI have been developed over the last few years, aimed to offer new parameters, which could be used as neuroimaging biomarkers. Each technique has shown pros and cons, but no gold standard exists yet. The fractal dimension (FD) has been investigated as a novel potential objective parameter for monitoring intratumoral space-filling properties of SWI patterns. We showed that SWI patterns found in different tumors or different glioma grades can be represented by a gradient in the fractal dimension, thereby enabling each tumor to be assigned a specific SWI fingerprint. Such results were especially relevant in the differentiation of low-grade versus high-grade gliomas, as well as from high-grade gliomas versus lymphomas.Therefore, FD has been suggested as a potential image biomarker to analyze intrinsic neoplastic architecture in order to improve the differential diagnosis within clinical neuroimaging, determine appropriate therapy, and improve outcome in patients.These promising preliminary findings could be extended into the field of neurotraumatology, by means of the application of computational fractal-based analysis for the qualitative and quantitative imaging of microbleedings in traumatic brain injury patients. In consideration of some evidences showing that SWI signals are correlated with trauma clinical severity, FD might offer some objective prognostic biomarkers.In conclusion, fractal-based morphometrics of SWI could be further investigated to be used in a complementary way with other techniques, in order to form a holistic understanding of the temporal evolution of brain tumors and follow-up response to treatment, with several further applications in other fields, such as neurotraumatology and cerebrovascular neurosurgery as well.

Traumatic Brain Injury Recovery with Photobiomodulation: Cellular Mechanisms, Clinical Evidence, and Future Potential.

Traumatic Brain Injury (TBI) remains a significant global health challenge, lacking effective pharmacological treatments. This shortcoming is attributed to TBI's heterogeneous and complex pathophysiology, which includes axonal damage, mitochondrial dysfunction, oxidative stress, and persistent neuroinflammation. The objective of this study is to analyze transcranial photobiomodulation (PBM), which employs specific red to near-infrared light wavelengths to modulate brain functions, as a promising therapy to address TBI's complex pathophysiology in a single intervention. This study reviews the feasibility of this therapy, firstly by synthesizing PBM's cellular mechanisms with each identified TBI's pathophysiological aspect. The outcomes in human clinical studies are then reviewed. The findings support PBM's potential for treating TBI, notwithstanding variations in parameters such as wavelength, power density, dose, light source positioning, and pulse frequencies. Emerging data indicate that each of these parameters plays a role in the outcomes. Additionally, new research into PBM's effects on the electrical properties and polymerization dynamics of neuronal microstructures, like microtubules and tubulins, provides insights for future parameter optimization. In summary, transcranial PBM represents a multifaceted therapeutic intervention for TBI with vast potential which may be fulfilled by optimizing the parameters. Future research should investigate optimizing these parameters, which is possible by incorporating artificial intelligence.

Life After Traumatic Brain Injury: Effects on the Lifestyle and Quality of Life of Community-Dwelling Patients.

Persons who have experienced traumatic brain injury (TBI) may encounter a range of changes in their physical, mental, and cognitive functions as well as high fatigue levels. To gain a comprehensive understanding of the challenges faced by persons after TBI, we conducted multi-domain assessments among community-dwelling persons with a history of TBI and compared them with age- and sex-matched controls from the Northeastern Taiwan Community Medicine Research Cohort between 2019 and 2021. A total of 168 persons with TBI and 672 non-TBI controls were not different in terms of demographics, comorbidities, and physiological features. However, compared with the non-TBI group, the TBI group had a distinct lifestyle that involved increased reliance on analgesics (6.9% vs. 15.0%, respectively; p = 0.001) and sleep aids (p = 0.008), which negatively affected their quality of life. Moreover, they consumed more coffee (p < 0.001), tea (p < 0.001), cigarettes (p = 0.002), and betel nuts (p = 0.032) than did the non-TBI group. Notably, the use of coffee had a positive effect on the quality of life of the TBI group (F = 4.034; p = 0.045). Further, compared with the non-TBI group, the TBI group had increased risks of sarcopenia (p = 0.003), malnutrition (p = 0.003), and anxiety (p = 0.029) and reduced blood levels of vitamin D (29.83 ± 10.39 vs. 24.20 ± 6.59 ng/mL, respectively; p < 0.001). Overall, the TBI group had a reduced health-related quality of life, with significant challenges related to physical health, mental well-being, social interactions, pain management, and fatigue levels. Moreover, the TBI group experienced poorer sleep quality and efficiency than did the non-TBI group. In conclusion, persons who have sustained brain injuries that require comprehensive and holistic care that includes lifestyle modification, mental and physical healthcare plans, and increased long-term support from their communities. ClinicalTrials.gov (identifier: NCT04839796).

Therapeutic potential of Lingjiao Gouteng decoction in acute alcohol intoxication and alcohol-induced brain injury involving the RhoA/ROCK2/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Alcohol misuse persists as a prevalent societal concern and precipitates diverse deleterious consequences, entailing significant associated health hazards including acute alcohol intoxication (AAI). Binge drinking, a commonplace pattern of alcohol consumption, may incite neurodegeneration and neuronal dysfunction. Clinicians tasked with managing AAI confront a dearth of pharmaceutical intervention alternatives. In contrast, natural products have garnered interest due to their compatibility with the human body and fewer side effects. Lingjiao Gouteng decoction (LGD), a classical traditional Chinese medicine decoction, represents a frequently employed prescription in cases of encephalopathy, although its efficacy in addressing acute alcoholism and alcohol-induced brain injury remains inadequately investigated. AIM OF THE STUDY: To investigate the conceivable therapeutic benefits of LGD in AAI and alcohol-induced brain injury, while delving into the underlying fundamental mechanisms involved. MATERIALS AND METHODS: We established an AAI mouse model through alcohol gavage, and LGD was administered to the mice twice at the 2 h preceding and 30 min subsequent to alcohol exposure. The study encompassed the utilization of the loss of righting reflex assay, histopathological analysis, enzyme-linked immunosorbent assays, and cerebral tissue biochemical assays to investigate the impact of LGD on AAI and alcohol-induced brain injury. These assessments included a comprehensive evaluation of various biomarkers associated with the inflammatory response and oxidative stress. Finally, RT-qPCR, Western blot, and immunofluorescence staining were carried out to explore the underlying mechanisms through which LGD exerts its therapeutic influence, potentially through the regulation of the RhoA/ROCK2/NF-κB signaling pathway. RESULTS: Our investigation underscores the therapeutic efficacy of LGD in ameliorating AAI, as evidenced by discernible alterations in the loss of righting reflex assay, pathological analysis, and assessment of inflammatory and oxidative stress biomarkers. Furthermore, the results of RT-qPCR, Western blot, and immunofluorescence staining manifest a noteworthy regulatory effect of LGD on the RhoA/ROCK2/NF-κB signaling pathway. CONCLUSIONS: The present study confirmed the therapeutic potential of LGD in AAI and alcohol-induced brain injury, and the protective effects of LGD against alcohol-induced brain injury may be intricately linked to the RhoA/ROCK2/NF-κB signaling pathway.

"I Wish I Had That!": A Qualitative Analysis of Psychosocial Treatment Preferences Among Young Adults With Recent Concussion and Anxiety.

OBJECTIVE: To assess psychosocial treatment preferences and factors that may affect treatment participation among young adults with a recent concussion and co-occurring anxiety. DESIGN: In-depth, semi-structured individual qualitative interviews, followed by thematic analysis using a hybrid deductive-inductive approach. SETTING: Academic medical center in the US Northeast. PARTICIPANTS: Seventeen young adults (18-24y) who sustained a concussion within the past 3-10 weeks and reported at least mild anxiety (≥5 on the Generalized Anxiety Disorder-7 questionnaire). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Primary outcomes include preferences for program content (eg, topics and skills), delivery modality, format, and barriers and facilitators to participation. RESULTS: We identified 4 domains characterizing participants' perceptions of and preferences for treatment. (1) Program content: Participants preferred a program early after injury that included psychoeducation and coping skills (eg, activity pacing, deep breathing, mindfulness). (2) Therapeutic processes: Participants preferred a person-centered approach in which clinicians normalized anxiety postconcussion and reassured them of recovery. (3) Program logistics: Participants endorsed that a brief, virtual program would be acceptable. They preferred access to program components through multiple modalities (eg, audio, video) and accommodations to manage concussion symptoms. (4) Barriers and facilitators to participation: Barriers included acute concussion symptoms (eg, screen sensitivity), time constraints, and forgetting sessions. Facilitators included a program that is flexible (format, scheduling), personalized (self-chosen mode for reminders, measure of accountability), and accessible (ie, advertising through health care professionals or social media). CONCLUSIONS: Participants need psychosocial support that normalizes their experiences and provides education and coping tools. Treatments should be accessible, flexible, and person centered. Psychosocial treatments meeting these preferences may help optimize the recovery of young adults with recent concussion and anxiety.

Nutritional Considerations of Irish Performance Dietitians and Nutritionists in Concussion Injury Management.

Sport-related concussion incidence has increased in many team-based sports, such as rugby, Gaelic (camogie, hurling, football), and hockey. Concussion disrupts athletes' brain function, causing an "energy crisis" that requires energy and nutrient support to restore function and heal. Performance dietitians and nutritionists play a role in supporting athletes' post-injury nutritional demands. This study aimed to investigate Irish performance dietitians' and nutritionists' knowledge and implementation of nutritional strategies to manage and support athletes' recovery following concussion. In-depth, semi-structured interviews were conducted with seventeen (n = 17) Irish performance dietitians and nutritionists recruited from the Sport and Exercise Nutrition register and other sporting body networks across Ireland. Participants practised or had practised with amateur and/or professional athletes within the last ten years. All interviews and their transcripts were thematically analysed to extract relevant insights. These data provided valuable insights revealing performance dietitians and nutritionists: (1) their awareness of concussion events and (2) their use of nutritional supports for concussion management. Furthermore, the research highlighted their implementation of 'novel nutritional protocols' specifically designed to support and manage athletes' concussion recovery. There was a clear contrast between participants who had an awareness and knowledge of the importance of nutrition for brain recovery after sport-related concussion(s) and those who did not. Participants presenting with a practical understanding mentioned re-emphasising certain foods and supplements they were already recommending to athletes in the event of a concussion. Performance dietitians and nutritionists were keeping up to date with nutrition research on concussions, but limited evidence has prevented them from implementing protocols in practice. Meanwhile, participants mentioned trialling/recommending nutritional protocols, such as carbohydrate reloading, reducing omega-6 intake, and acutely supplementing creatine, omega-3 fish oils high in Docosahexaenoic acid, and probiotics to support brain healing. Performance dietitians' and nutritionists' use of nutrition protocols with athletes following concussion was linked to their knowledge and the limited scientific evidence available. Nutrition implementation, therefore, may be overlooked or implemented with uncertainty, which could negatively affect athletes' recovery following sports-related concussions.

Are Tai Chi and Qigong effective in the treatment of traumatic brain injury? A systematic review.

BACKGROUND: Traumatic brain injury (TBI) adversely affects both young and old and is a growing public health concern. The common functional, psychological, and cognitive changes associated with TBI and recent trends in its management, such as recommending sub-threshold aerobic activity, and multi-modal treatment strategies including vestibular rehabilitation, suggest that Tai Chi/Qigong could be beneficial for TBI. Tai Chi and Qigong are aerobic mind-body practices with known benefits for maintaining health and mitigating chronic disease. To date, no systematic review has been published assessing the safety and effectiveness of Tai Chi/Qigong for traumatic injury. METHODS: The following databases were searched: MEDLINE, CINAHL Cochrane Library, Embase, China National Knowledge Infrastructure Database, Wanfang Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. All people with mild, moderate, or severe TBI who were inpatients or outpatients were included. All Types of Tai Chi and Qigong, and all comparators, were included. All measured outcomes were included. A priori, we chose "return to usual activities" as the primary outcome measure as it was patient-oriented. Cochrane-based risk of bias assessments were conducted on all included trials. Quality of evidence was assessed using the grading of recommendation, assessment, development, and evaluation (GRADE) system. RESULTS: Five trials were assessed; three randomized controlled trials (RCTs) and two non-RCTs; only two trials were conducted in the last 5 years. No trial measured "return to normal activities" or vestibular status as an outcome. Four trials - two RCTs and two non-RCTS - all found Tai Chi improved functional, psychological and/or cognitive outcomes. One RCT had a low risk of bias and a high level of certainty; one had some concerns. One non-RCTs had a moderate risk of bias and the other a serious risk of bias. The one Qigong RCT found improved psychological outcomes. It had a low risk of bias and a moderate level of certainty. Only one trial reported on adverse events and found that none were experienced by either the exercise or control group. CONCLUSION: Based on the consistent finding of benefit in the four Tai Chi trials, including one RCT that had a high level of certainty, there is a sufficient signal to merit conducting a large, high quality multi-centre trial on Tai Chi for TBI and test it against current trends in TBI management. Based on the one RCT on TBI and Qigong, an additional confirmatory RCT is indicated. Further research is indicated that reflects current management strategies and includes adverse event documentation in both the intervention and control groups. However, these findings suggest that, in addition to Tai Chi's known health promotion and chronic disease mitigation benefits, its use for the treatment of injury, such as TBI, is potentially a new frontier. SYSTEMATIC REVIEW REGISTRATION: PROSPERO [ CRD42022364385 ].

Non-pharmacological interventions for sleep disruptions and fatigue after traumatic brain injury: a scoping review.

OBJECTIVE: The aim of this study was to conduct a scoping review to determine the nature, variety, and volume of empirical evidence on nonpharmacological interventions for sleep disturbances with potential implications for fatigue in adults sustaining a traumatic brain injury (TBI). METHODS: A systematic literature search was conducted across four databases to identify primary studies testing a single non-pharmacological intervention or a combination of non-pharmacological interventions for sleep disturbances and fatigue in community-dwelling adults with TBI. RESULTS: Sixteen studies were reviewed addressing six non-pharmacological interventions for sleep disruptions and fatigue after TBI including light therapy, cognitive-behavioral therapy, warm footbath application, shiatsu, and sleep hygiene protocol. Non-pharmacological interventions involving light or cognitive-behavioral therapy were reported in 75% of the studies. Actigraphy-based estimation of total sleep time and subjective level of fatigue were frequent outcomes. CONCLUSION: While this scoping review has utility in describing existing non-pharmacological approaches to manage sleep and fatigue after TBI, the findings suggest that interventions are often developed without considering TBI individuals' source of motivation and the need for support in self-administration. Future studies may achieve greater sustainability by considering the evolving needs of TBI patients and their families and the drivers and barriers that might influence non-pharmacological intervention use at home.

Dehydroevodiamine ameliorates neurological dysfunction after traumatic brain injury in mice via regulating the SIRT1/FOXO3a/Bim pathway.

BACKGROUND: Traumatic Brain Injury (TBI) poses a considerable public health challenge, resulting in mortality, disability, and economic strain. Dehydroevodiamine (DEDM) is a natural compound derived from a traditional Chinese herbal medicine. Prior studies have substantiated the neuroprotective attributes of this compound in the context of TBI. Nevertheless, a comprehensive comprehension of the exact mechanisms responsible for its neuroprotective effects remains elusive. It is imperative to elucidate the precise intrinsic mechanisms underlying the neuroprotective actions of DEDM. PURPOSE: The aim of this investigation was to elucidate the mechanism underlying DEDM treatment in TBI utilizing both in vivo and in vitro models. Specifically, our focus was on comprehending the impact of DEDM on the Sirtuin1 (SIRT1) / Forkhead box O3 (FOXO3a) / Bcl-2-like protein 11 (Bim) pathway, a pivotal player in TBI-induced cell death attributed to oxidative stress. STUDY DESIGN AND METHODS: We established a TBI mouse model via the weight drop method. Following continuous intraperitoneal administration, we assessed the neurological dysfunction using the Modified Neurological Severity Score (mNSS) and behavioral assay, followed by sample collection. Secondary brain damage in mice was evaluated through Nissl staining, brain water content measurement, Evans blue detection, and Western blot assays. We scrutinized the expression levels of oxidative stress-related indicators and key proteins for apoptosis. The intricate mechanism of DEDM in TBI was further explored through immunofluorescence, Co-immunoprecipitation (Co-IP) assays, real-time quantitative PCR (RT-qPCR), dual-luciferase assays and western blotting. Additionally, we further investigated the specific therapeutic mechanism of DEDM in an oxidative stress cell model. RESULTS: The results indicated that DEDM effectively ameliorated oxidative stress and apoptosis post-TBI, mitigating neurological dysfunction and brain injury in mice. DEDM facilitated the deacetylation of FOXO3a by up-regulating the expression of the deacetylase SIRT1, consequently suppressing Bim expression. This mechanism contributed to the alleviation of neurological injury and symptom improvement in TBI-afflicted mice. Remarkably, SIRT1 emerged as a central mediator in the overall treatment mechanism. CONCLUSIONS: DEDM exerted significant neuroprotective effects on TBI mice by modulating the SIRT1/FOXO3a/Bim pathway. Our innovative research provides a basis for further exploration of the clinical therapeutic potential of DEDM in the context of TBI.