Electroacupuncture improves cognitive function in a rat model of mild traumatic brain injury by regulating the SIRT-1/PGC-1α/mitochondrial pathway.

BACKGROUND: Mild traumatic brain injury (mTBI) is a common neurological trauma that can lead to cognitive impairment. The sirtuin-1 (SIRT-1)/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) pathway has been reported to have neuroprotective effects in rats with craniocerebral injury. We evaluated potential mechanisms underlying electroacupuncture-mediated recovery of cognitive function after mTBI, focusing on the SIRT-1/PGC-1α/mitochondrial pathway. METHODS: We included forty 6-week-old male Sprague-Dawley rats in this study. Rats were randomly divided into four groups: controlled cortical impactor (CCI, n = 10), sham operation (sham, n = 10), electroacupuncture-treated CCI (CCI+EA, n = 10), and electroacupuncture-treated sham (sham+EA, n = 10) group. Randomization was performed by assigning a random number to each rat and using a random number table. The mTBI rat model was established using a controllable cortical impactor. Electroacupuncture therapy was performed on the back of rats, by inserting acupuncture needles to the specific acupoints and setting appropriate parameters for treatment. We evaluated spatial learning and memory functions with the Morris water maze test. We performed quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, adenosine triphosphate (ATP) determination, and mitochondrial respiratory chain complex I (MRCC I) determination on rat hippocampal tissue. We analyzed SIRT-1/PGC-1α expression levels and the results of mitochondrial function assays, and compared differences between groups using bilateral Student's t -tests. RESULTS: Compared with the sham group, SIRT-1/PGC-1α expression was downregulated in the hippocampus of CCI group ( P <0.01). Although this expression was upregulated following electroacupuncture, it did not reach the levels observed in the sham group ( P <0.05). Compared with the sham group, MRCC I and ATP levels in the CCI group were significantly reduced, and increased after electroacupuncture ( P <0.01). In the Morris water maze, electroacupuncture reduced the incubation period of rats and increased average speed and number of crossing platforms ( P <0.05). CONCLUSION: Electroacupuncture may improve cognitive function in the mTBI rat model by regulating the SIRT-1/PGC-1α/mitochondrial pathway.

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.

Treatment of chronic symptoms following mild traumatic brain injury with transcranial LED: a sham run-in pilot study of photobiomodulation therapy.

PRIMARY OBJECTIVE: We evaluated whether photobiomodulation with red/near infrared light applied transcranially via light emitting diodes (LED) was associated with reduced symptoms and improved cognitive functioning in patients with chronic symptoms following mild traumatic brain injury. RESEARCH DESIGN: Participants (3 men, 6 women; 22-61 years-old) underwent a 6-week intervention involving 18 40-minute transcranial LED treatment sessions. METHODS AND PROCEDURES: Reliable change indices were calculated for 10 neuropsychological test scores and 3 self-report questionnaires of subjective cognition, post-concussion symptoms, and depression at baseline and following treatment. Questionnaires were also administered after 2-week sham and at 1-month and 2-month follow-ups. MAIN OUTCOME AND RESULTS: Only 2 participants improved on neuropsychological testing. On questionnaires, 4 reported improved cognition, 5 reported improved post-concussion symptoms, and 3 reported improved depression. Significant improvement in 2 or more domains was reported by 4 participants and mostly maintained at both follow-ups. CONCLUSIONS: Most participants did not improve on neuropsychological testing. A minority self-reported improvement in symptoms, potentially explained by the intervention, psychiatric medication changes, placebo effects, or other factors. Selecting participants with different clinical characteristics, and dosing and delivery system changes, may produce different results. A study design accounting for placebo effects appears warranted in future trials.

Mild Traumatic Brain Injuries and Risk for Affective and Behavioral Disorders.

OBJECTIVES: Recent studies document an association between mild traumatic brain injuries (mTBIs) in children and postinjury psychiatric disorders. However. these studies were subject to limitations in the design, lack of long-term follow-up, and poorly defined psychiatric outcomes. This study determines the incidence and relative risk of postinjury new affective and behavior disorders 4 years after mTBIs. METHODS: A cohort study of mTBI cases and matched comparisons within an integrated health care system. The mTBI group included patients ≤17 years of age, diagnosed with mTBI from 2000 to 2014 (N = 18 917). Comparisons included 2 unexposed patients (N = 37 834) per each mTBI-exposed patient, randomly selected and matched for age, sex, race/ethnicity, and date of medical visit (reference date to mTBI injury). Outcomes included a diagnosis of affective or behavioral disorders in the 4 years after mTBI or the reference date. RESULTS: Adjusted risks for affective disorders were significantly higher across the first 3 years after injury for the mTBI group, especially during the second year, with a 34% increase in risk. Adjusted risks for behavioral disorders were significant at years 2 and 4, with up to a 37% increase in risk. The age group with the highest risk for postinjury affective and behavioral disorders was 10- to 13-year-old patients. CONCLUSIONS: Sustaining an mTBI significantly increased the risks of having a new affective or behavioral disorder up to 4 years after injury. Initial and ongoing screening for affective and behavior disorders following an mTBI can identify persistent conditions that may pose barriers to recovery.

Early intervention treatment in the first 2 weeks following concussion in adults: A systematic review of randomised controlled trials.

OBJECTIVE: International guidelines support a repertoire of therapeutic interventions that may assist recovery following concussion. We aimed to systematically review the efficacy of early pharmacological and non-pharmacological interventions initiated within two weeks of injury on symptoms and functional recovery of adults with concussion. METHODS: We conducted a Systematic Review (SR) of Randomised Controlled Trials (RCTs) without meta-analysis utilising the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was performed of four databases. Study inclusion criteria were adult participants diagnosed with concussion and commencing active intervention within 14 days of injury. RESULTS AND CONCLUSIONS: Of 7531 studies identified, 11 were included in the final review. Six studies were rated as high-risk of bias, three with some concerns and two as low-risk of bias. We found no evidence to support specific pharmacotherapeutic management to hasten the natural recovery time-course. Two studies reported significant improvement in selected concussion symptoms following manual therapy (at 48-72 hours post-treatment) or telephone counselling interventions (at 6 months post-injury). No high quality RCTs demonstrate superior effects of early therapeutic interventions on concussion recovery in the first 2 weeks. We advocate future research to examine impacts of health-clinician contact points aligned with symptom-specific interventions.

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial Evaluating Transcranial Photobiomodulation as Treatment for Concussion.

INTRODUCTION: Literature indicating that transcranial photobiomodulation (tPBM) may enable the brain to recover normal function after concussion, resulting in symptoms reduction, and improved cognitive function after concussion is limited by small sample sizes and lack of controls. METHODS: We conducted a randomized, double-blind, placebo-controlled trial examining the effect of 6 wk of tPBM in patients 11 yr or older who received care for persistent postconcussion symptoms between September 2012 and December 2015. Our primary outcome measure was the mean difference in Postconcussion Symptom Scale total score and the raw Immediate Postconcussion Assessment and Cognitive Testing composite scores between study entry and treatment completion. Participants received two, 10-min sessions either with tPBM units or via two placebo units, three times per week. We screened for potential confounding variables using univariable analyses. We entered covariables that differed between the two groups on univariable screening into a regression analysis. We considered adjusted odds ratio that did not cross one statistically significant. RESULTS: Forty-eight participants completed the study. Most were female (63%), and a majority sustained their injury during sports or exercise (71%). Despite randomization, those that received tPBM therapy reported a greater number of previous concussions. After adjusting for the effect of previous concussions and multiple comparisons, there were no significant differences between tPBM and placebo groups at 3 or 6 wk of treatment. CONCLUSIONS: Despite showing promise in previous investigations, our study did not show benefit to tPBM over placebo therapy in patients experiencing persistent postconcussion symptoms. Further investigation is needed to determine if varying the dose or timing alters the efficacy of tPBM after concussion.

Efficacy and safety of acupuncture in the treatment of post-traumatic headache secondary to mild traumatic brain injury: A systematic evaluation and meta-analysis protocol of randomized controlled trials.

INTRODUCTION: Post-traumatic headache secondary to mild traumatic brain injury in patients has become an important factor in their prognosis. Due to the lack of effective pharmacological treatments, non-pharmacological interventions such as acupuncture are considered to have greater potential. However, the efficacy and safety of acupuncture treatment have not been clearly demonstrated. The purpose of this meta-analysis protocol is to investigate the effectiveness and safety of acupuncture in the treatment of headache secondary to mild traumatic brain injury. METHODS AND ANALYSIS: Seven English and Chinese databases will be selected and searched according to their respective search methods, spanning the period from database creation to April 2022, and the languages will be limited to English and Chinese. Only randomized controlled trials will be included. Study selection, data collection, and risk of bias control will be performed by two independent investigators. Any disagreements will be referred to a third independent investigator for decision and documentation. Revman software will be used to complete our meta-analysis, and risk of bias assessment, subgroup analysis, and sensitivity analysis will be performed to correct the results. Finally we will assess the reliability of our final results using the Recommended Guidelines Development Tool for Assessment. ETHICS AND DISSEMINATION: All data for this study will be obtained from published journals, so no ethical review will be required. The completed review will be published in a peer-reviewed journal and the findings will be further disseminated through presentation at an appropriate forum or conference.

A Potential Role Exists for Nutritional Interventions in the Chronic Phase of Mild Traumatic Brain Injury, Concussion and Sports-Related Concussion: A Systematic Review.

Mild traumatic brain injury (mTBI) represents a significant burden for individuals, economies, and healthcare systems worldwide. Recovery protocols focus on medication and physiotherapy-based interventions. Animal studies have shown that antioxidants, branched-chain amino acids and omega-3 fatty acids may improve neurophysiological outcomes after TBI. However, there appears to be a paucity of nutritional interventions in humans with chronic (≥1 month) symptomology post-mTBI. This systematic literature review aimed to consolidate evidence for nutrition and dietary-related interventions in humans with chronic mTBI. The review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021277780) and conducted following the Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three reviewers searched five databases (PubMed/MEDLINE, Web of Science, SPORTDiscus, CINAHL Complete and Cochrane), which yielded 6164 studies. Nine studies met the inclusion criteria. The main finding was the lack of interventions conducted to date, and a quality assessment of the included studies was found to be fair to good. Due to heterogeneity, a meta-analysis was not feasible. The six nutrition areas identified (omega-3 fatty acids, melatonin, Enzogenol®, MLC901, ketogenic diet and phytocannabinoids) were safe and well-tolerated. It was found that these nutritional interventions may improve cognitive failures, sleep disturbances, anxiety, physical disability, systolic blood pressure volume and sport concussion assessment tool scores following mTBI. Potential areas of improvement identified for future studies included blinding, reporting compliance, and controlling for confounders. In conclusion, further research of higher quality is needed to investigate the role of nutrition in recovery from mTBI to reduce the burden of chronic outcomes following mTBI.

HBOT has a better cognitive outcome than NBH for patients with mild traumatic brain injury: A randomized controlled clinical trial.

BACKGROUND: Normobaric hyperoxia (NBH) and hyperbaric oxygen therapy (HBOT) are effective treatment plan for traumatic brain injury (TBI). The aim of this study was to compare cognitive outcome after mild TBI between NBH and HBOT so as to provide a more suitable treatment strategy for patients with mild TBI. METHODS: A prospective research was conducted between October 2017 and March 2023, enrolling patients with mild TBI (Glasgow coma scale score: 13-15 points) within 24 hours of injury in Cangzhou Central Hospital. Patients were randomized into 3 groups: group control (C), group NBH and group HBOT. The patients in HBOT group received hyperbaric oxygen therapy in high pressure oxygen chamber and patients in NBH group received hyperbaric oxygen therapy. at 0 minute before NBH or HBOT (T1), 0 minute after NBH or HBOT (T2) and 30 days after NBH or HBOT (T3), level of S100ß, NSE, GFAP, HIF-1α, and MDA were determined by ELISA. At the same time, the detection was performed for MoCA and MMSE scores, along with rSO2. RESULTS: The results showed both NBH and HBOT could improve the score of MoCA and MMSE, as well as the decrease the level of S100ß, NSE, GFAP, HIF-1α, MDA, and rSO2 compared with group C. Furthermore, the patients in group HBOT have higher score of MoCA and MMSE and lower level of S100ß, NSE, GFAP, HIF-1α, MDA, and rSO2. CONCLUSION: Both NBH and HBOT can effectively improve cognitive outcome for patients with mild TBI by improving cerebral hypoxia and alleviating brain injury, while HBOT exert better effect than NBH.

Cessations of consciousness in meditation: Advancing a scientific understanding of nirodha samapatti.

Absence of consciousness can occur due to a concussion, anesthetization, intoxication, epileptic seizure, or other fainting/syncope episode caused by lack of blood flow to the brain. However, some meditation practitioners also report that it is possible to undergo a total absence of consciousness during meditation, lasting up to 7 days, and that these "cessations" can be consistently induced. One form of extended cessation (i.e., nirodha samapatti) is thought to be different from sleep because practitioners are said to be completely impervious to external stimulation. That is, they cannot be 'woken up' from the cessation state as one might be from a dream. Cessations are also associated with the absence of any time experience or tiredness, and are said to involve a stiff rather than a relaxed body. Emergence from meditation-induced cessations is said to have profound effects on subsequent cognition and experience (e.g., resulting in a sudden sense of clarity, openness, and possibly insights). In this paper, we briefly outline the historical context for cessation events, present preliminary data from two labs, set a research agenda for their study, and provide an initial framework for understanding what meditation induced cessation may reveal about the mind and brain. We conclude by integrating these so-called nirodha and nirodha samapatti experiences-as they are known in classical Buddhism-into current cognitive-neurocomputational and active inference frameworks of meditation.

Osteopathic manipulative treatment for concussions and postconcussive syndrome in athletes: a literature review.

CONTEXT: Concussions are the most common type of traumatic brain injury (TBI) and can often occur in athletes. These injuries have many deleterious acute symptoms and can lead to the development of postconcussive syndrome (PCS). Osteopathic manipulative treatment (OMT) is a treatment option that may benefit patients with concussions and PCS. OBJECTIVES: The objective of this review is to determine whether OMT can improve symptoms associated with concussions and PCS in athletes. METHODS: A comprehensive literature review was conducted between August 2021 and March 2022 by two authors (Z.K.L. and K.D.T.) who searched the literature utilizing PubMed, Google Scholar, and Cochrane Library. Articles reviewed included case reports, case studies, randomized control trials, meta-analyses, and peer-reviewed journal articles. Search terms included concussion, postconcussive symptoms, osteopathic manipulative medicine, and manipulation. To be included into this study, articles must have included OMT from an osteopathic physician or manipulative techniques by nonosteopathic providers for patients with a concussion or PCS, and the insulting injury must have occurred in an athletic setting. No disagreements occurred between authors about what studies to include. However, we were prepared to come to a unanimous decision through discussion among the authors. A narrative synthesis was performed. No other data analyses were conducted in this study. RESULTS: Included in this review were nine articles including randomized control trials, retrospective review, case series, longitudinal, retrospective studies, and case reports. The literature shows the positive effects of OMT and manipulative techniques on symptom resolution after a concussion. However, most of the literature is qualitative rather than quantitative in nature, lacking in randomized control trials. CONCLUSIONS: There is a scarcity of high-quality studies evaluating the effectiveness of OMT on concussions and PCS. More research is needed to understand the degree of benefit for this treatment option.

Heart Rate Variability Biofeedback for Mild Traumatic Brain Injury: A Randomized-Controlled Study.

To determine whether heart rate variability biofeedback (HRV-BF) training, compared to a psychoeducation control condition can strengthen the integration of the central and autonomic nervous systems as measured by neuropsychological measures in patients with mild traumatic brain injury (mTBI). Participants were recruited from two university hospitals in Taipei, Taiwan. A total of 49 participants with mTBI were recruited for this study. Forty-one participants completed the study, 21 in the psychoeducation group and 20 in the HRV-BF group. Randomized controlled study. The Taiwanese Frontal Assessment Battery, the Semantic Association of Verbal Fluency Test, the Taiwanese version of the Word Sequence Learning Test, the Paced Auditory Serial Addition Test-Revised, and the Trail Making Test were used as performance-based neuropsychological functioning measures. The Checklist of Post-concussion Symptoms, the Taiwanese version of the Dysexecutive Questionnaire, the Beck Anxiety Inventory, the Beck Depression Inventory, and the National Taiwan University Irritability Scale were used as self-report neuropsychological functioning measures. Furthermore, heart rate variability pre- vs. post-training was used to measure autonomic nervous system functioning. Executive, information processing, verbal memory, emotional neuropsychological functioning, and heart rate variability (HRV) were improved significantly in the HRV-BF group at the posttest whereas the psychoeducation group showed no change. HRV biofeedback is a feasible technique following mild TBI that can improve neuropsychological and autonomic nervous system functioning. HRV-BF may be clinically feasible for the rehabilitation of patients with mTBI.

Neuroprotective Effect of Sub-lethal Hyperthermia Preconditioning in a Rat Model of Repeated Closed Head Injury.

Repeated mild traumatic brain injury (rTBI), one of the most common forms of traumatic brain injury, is a worldwide severe public health concern. rTBI induces cumulative neuronal injury, neurological dysfunction, and cognitive deficits. Although there are clinical treatment methods, there is still an urgent need to develop preventive approaches for susceptible populations. Using a repeated closed head injury (rCHI) rat model, we interrogate the effect of sub-lethal hyperthermia preconditioning (SHP) on rCHI-induced neuronal injury and behavioral changes. Our study applied the repeated weight-drop model to induce the rCHI. According to the changes of heat shock protein 70 (HSP 70) in the cortex and hippocampus following a single SHP treatment in normal rats, the SHP was delivered to the rats 18 h before rCHI. We found that HSP significantly alleviated rCHI-induced anxiety-like behaviors and impairments in motor abilities and spatial memory. SHP exerts significant neuroprotection against rCHI-induced neuronal damage, apoptosis, and neuroinflammation. Our findings support the potential use of SHP as a preventative approach for alleviating rCHI-induced brain damage.

Follow-up visits after a concussion in the pediatric population: An integrative review.

BACKGROUND: Concussions are a significant health issue for children and youth. After a concussion diagnosis, follow-up visits with a health care provider are important for reassessment, continued management, and further education. OBJECTIVE: This review aimed to synthesize and analyse the current state of the literature on follow-up visits of children with a concussive injury and examine the factors associated with follow-up visits. METHODS: An integrative review was conducted based on Whittemore and Knafl's framework. Databases searched included PubMed, MEDLINE, CINAHL, PsycINFO, and Google Scholar. RESULTS: Twenty-four articles were reviewed. We identified follow-up visit rates, timing to a first follow-up visit, and factors associated with follow-up visits as common themes. Follow-up visit rates ranged widely, from 13.2 to 99.5%, but time to the first follow-up visit was only reported in eight studies. Three types of factors were associated with attending a follow-up visit: injury-related factors, individual factors, and health service factors. CONCLUSION: Concussed children and youth have varying rates of follow-up care after an initial concussion diagnosis, with little known about the timing of this visit. Diverse factors are associated with the first follow-up visit. Further research on follow-up visits after a concussion in this population is warranted.

Yoga and Mindfulness Intervention for Concussion Recovery.

Concussion imposes a substantial global health burden, and few evidence-based treatments that approach concussion treatment holistically are available. Moreover, early intervention is important before concussion symptoms become chronic and more refractory to treatment. In this pilot study, we evaluated the tolerability of a protocol called Mindfulness and Yoga for Treatment After Concussion (MYTAC), which was specifically designed for individuals with concussion. We also explored the possible benefit of the MYTAC protocol for concussion recovery. Participants were 15-60 years old with recent concussion and had presented to selected practices within a university health system. Participants used the video-based MYTAC protocol for 5 consecutive days and reported concussion symptoms on an abbreviated version of the Sports Concussion Assessment Tool version 3 (SCAT3). We compared the abbreviated SCAT3 scores across the intervention period, including immediately before and after each yoga session, using standard statistical methods for paired data. Of 25 participants enrolled in the study, 15 completed the MYTAC protocol and 1 completed 2 days of the protocol before withdrawing due to worsening symptoms; the remaining 9 participants did not complete the protocol. On average, total abbreviated SCAT3 scores decreased by 9.9 ± 7.6 points, or approximately 50%, over the intervention period (from an initial value of 18.8 ± 6.7 points prior to the yoga protocol). Although this pilot study had significant methodological limitations, we concluded that the MYTAC protocol had fair tolerability and possibly a beneficial effect on concussion recovery. However, future interventions should evaluate this protocol in larger, more rigorously designed studies.

A Framework for Understanding the Contribution of Psychosocial Factors in Biopsychosocial Explanatory Models of Persistent Postconcussion Symptoms.

Biopsychosocial models are currently used to explain the development of persistent postconcussion symptoms (PPCS) following concussion. These models support a holistic multidisciplinary management of postconcussion symptoms. One catalyst for the development of these models is the consistently strong evidence pertaining to the role of psychological factors in the development of PPCS. However, when applying biopsychosocial models in clinical practice, understanding and addressing the influence of psychological factors in PPCS can be challenging for clinicians. Accordingly, the objective of this article is to support clinicians in this process. In this Perspective article, we discuss current understandings of the main psychological factors involved in PPCS in adults and summarize these into 5 interrelated tenets: preinjury psychosocial vulnerabilities, psychological distress following concussion, environment and contextual factors, transdiagnostic processes, and the role of learning principles. With these tenets in mind, an explanation of how PPCS develop in one person but not in another is proposed. The application of these tenets in clinical practice is then outlined. Guidance is provided on how these tenets can be used to identify psychosocial risk factors, derive predictions, and mitigate the development of PPCS after concussion from a psychological perspective within biopsychosocial conceptualizations. IMPACT: This Perspective helps clinicians apply biopsychosocial explanatory models to the clinical management of concussion, providing summary tenets that can guide hypothesis testing, assessment, and treatment.

Immunocal® limits gliosis in mouse models of repetitive mild-moderate traumatic brain injury.

Successive traumatic brain injuries (TBIs) exacerbate neuroinflammation and oxidative stress. No therapeutics exist for populations at high risk of repetitive mild TBIs (rmTBIs). We explored the preventative therapeutic effects of Immunocal®, a cysteine-rich whey protein supplement and glutathione (GSH) precursor, following rmTBI and repetitive mild-moderate TBI (rmmTBI). Populations that suffer rmTBIs largely go undiagnosed and untreated; therefore, we first examined the potential therapeutic effect of Immunocal® long-term following rmTBI. Mice were treated with Immunocal® prior to, during, and following rmTBI induced by controlled cortical impact until analysis at 2 weeks, 2 months, and 6 months following the last rmTBI. Astrogliosis and microgliosis were measured in cortex at each time point and edema and macrophage infiltration by MRI were analyzed at 2 months post-rmTBI. Immunocal® significantly reduced astrogliosis at 2 weeks and 2 months post-rmTBI. Macrophage activation was observed at 2 months post-rmTBI but Immunocal® had no significant effect on this endpoint. We did not observe significant microgliosis or edema after rmTBI. The dosing regimen was repeated in mice subjected to rmmTBI; however, using this experimental paradigm, we examined the preventative therapeutic effects of Immunocal® at a much earlier timepoint because populations that suffer more severe rmmTBIs are more likely to receive acute diagnosis and treatment. Increases in astrogliosis, microgliosis, and serum neurofilament light (NfL), as well as reductions in the GSH:GSSG ratio, were observed 72 h post-rmmTBI. Immunocal® only significantly reduced microgliosis after rmmTBI. In summary, we report that astrogliosis persists for 2 months post-rmTBI and that inflammation, neuronal damage, and altered redox homeostasis present acutely following rmmTBI. Immunocal® significantly limited gliosis in these models; however, its neuroprotection was partially overwhelmed by repetitive injury. Treatments that modulate distinct aspects of TBI pathophysiology, used in combination with GSH precursors like Immunocal®, may show more protection in these repetitive TBI models.

The neuroprotective effect of electro-acupuncture on cognitive recovery for patients with mild traumatic brain injury: A randomized controlled clinical trial.

BACKGROUND: Traumatic brain injury (TBI) is a major health and socioeconomic problem that affects all societies. Consciousness disorder is a common complication after TBI while there is still no effective treatment currently. The aim of this study was to investigate the protective effect of electro-acupuncture (EA) on cognitive recovery for patients with mild TBI. METHODS: A total of 83 patients with initial Glasgow coma scale score higher than 12 points were assigned into this study. Then patients were randomly divided into 2 groups: EA group and control group (group C). Patients in group EA received EA treatment at Neiguan and Shuigou for 2 weeks. At 0 minute before EA treatment (T1), 0 minute after EA treatment (T2), and 8 weeks after EA treatment (T3), level of neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), hypoxia inducible factor-1α (HIF-1α), and malondialdehyde were tested by enzyme-linked immunosorbent assay. The score of Montreal Cognitive Function Assessment (MoCA) and mini-mental state examination (MMSE) as well as cerebral oxygen saturation (rSO2) were detected at the same time. RESULTS: Compared with the baseline at T1, the level of NSE, GFAP, HIF-1α, MDA, and rSO2 decreased, and the score of MoCA and MMSE increased in the 2 groups were significantly increased at T2-3 (P < .05). Compared with group C, the level of NSE, GFAP, HIF-1α, MDA, and rSO2 decreased, and the score of MoCA and MMSE increased were significantly increased at T2-3 in group EA; the difference were statistically significant (P < .05). CONCLUSIONS: EA treatment could improve the cognitive recovery for patients with mild TBI and the potential mechanism may be related to improving cerebral hypoxia and alleviating brain injury.

Neck Symptoms and Associated Clinical Outcomes in Patients Following Concussion.

OBJECTIVE: To examine the frequency and association of neck pain symptoms in patients with a concussion. STUDY SETTING AND PARTICIPANTS: Three-hundred and thirty-one consecutively enrolled patients aged 9 to 68 years with a diagnosed concussion 1 to 384 days post-injury were enrolled at a concussion clinic from a single integrated healthcare system in Western Pennsylvania between 2019 and 2021. DESIGN: Retrospective cohort analysis of prospectively collected concussion screening tool intake survey responses and clinical outcomes data. The primary outcome was self-reported neck pain or difficulty with neck movement on the Concussion Clinical Profiles Screening (CP Screen) tool, recovery time, and incidence of treatment referral. Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) composite scores, Vestibular/Ocular Motor Screening (VOMS) item scores, type and severity of neck symptoms, mechanism of injury, time from injury to clinic presentation, medical history, and concussion symptom profile were secondary outcomes. RESULTS: Of the 306 consecutively enrolled eligible patients in the registry, 145 (47%) reported neck pain, 68 (22.2%) reported difficulty moving their neck, and 146 (47.7%) reported either symptom. A total of 47 (15.4%) participants reported more severe neck symptoms, and this group took longer to recover (40 ± 27 days) than those not reporting neck symptoms (30 ± 28 days; U = 8316, P < .001). Stepwise logistic regression predicting more severe neck symptoms was significant (Nagelkerke R2 = 0.174, χ 2 = 9.315, P = .316) with older age ( P = .019) and mechanism of injury including motor vehicle collisions (MVCs) ( P = .047) and falls ( P = .044) as risk factors. MVCs and falls were associated with over 4 times and 2 times greater risk, respectively, for reporting more severe neck symptoms. CONCLUSION: Neck pain and stiffness symptoms are common in patients with a concussion following high-energy mechanisms of injury including MVCs or falls from height. These symptoms are associated with prolonged recovery. Providers should evaluate neck symptoms and consider targeted treatment strategies to limit their effects in patients with a concussion.

Acute thalamic connectivity precedes chronic post-concussive symptoms in mild traumatic brain injury.

Chronic post-concussive symptoms are common after mild traumatic brain injury (mTBI) and are difficult to predict or treat. Thalamic functional integrity is particularly vulnerable in mTBI and may be related to long-term outcomes but requires further investigation. We compared structural MRI and resting state functional MRI in 108 patients with a Glasgow Coma Scale (GCS) of 13-15 and normal CT, and 76 controls. We examined whether acute changes in thalamic functional connectivity were early markers for persistent symptoms and explored neurochemical associations of our findings using PET data. Of the mTBI cohort, 47% showed incomplete recovery 6 months post-injury. Despite the absence of structural changes, we found acute thalamic hyperconnectivity in mTBI, with specific vulnerabilities of individual thalamic nuclei. Acute fMRI markers differentiated those with chronic post-concussive symptoms, with time- and outcome-dependent relationships in a sub-cohort followed longitudinally. Moreover, emotional and cognitive symptoms were associated with changes in thalamic functional connectivity to known serotonergic and noradrenergic targets, respectively. Our findings suggest that chronic symptoms can have a basis in early thalamic pathophysiology. This may aid identification of patients at risk of chronic post-concussive symptoms following mTBI, provide a basis for development of new therapies and facilitate precision medicine application of these therapies.