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.

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.

A Review of Electrolyte, Mineral, and Vitamin Changes After Traumatic Brain Injury.

INTRODUCTION: Despite the prevalence of traumatic brain injury (TBI) in both civilian and military populations, the management guidelines developed by the Joint Trauma System involve minimal recommendations for electrolyte physiology optimization during the acute phase of TBI recovery. This narrative review aims to assess the current state of the science for electrolyte and mineral derangements found after TBI. MATERIALS AND METHODS: We used Google Scholar and PubMed to identify literature on electrolyte derangements caused by TBI and supplements that may mitigate secondary injuries after TBI between 1991 and 2022. RESULTS: We screened 94 sources, of which 26 met all inclusion criteria. Most were retrospective studies (n = 9), followed by clinical trials (n = 7), observational studies (n = 7), and case reports (n = 2). Of those, 29% covered the use of some type of supplement to support recovery after TBI, 28% covered electrolyte or mineral derangements after TBI, 16% covered the mechanisms of secondary injury after TBI and how they are related to mineral and electrolyte derangements, 14% covered current management of TBI, and 13% covered the potential toxic effects of the supplements during TBI recovery. CONCLUSIONS: Knowledge of mechanisms and subsequent derangements of electrolyte, mineral, and vitamin physiology after TBI remains incomplete. Sodium and potassium tended to be the most well-studied derangements after TBI. Overall, data involving human subjects were limited and mostly involved observational studies. The data on vitamin and mineral effects were limited, and targeted research is needed before further recommendations can be made. Data on electrolyte derangements were stronger, but interventional studies are needed to assess causation.

Characterizing Extreme Phenotypes for Perceived Improvement From Treatment in Persons With Chronic Pain Following Traumatic Brain Injury: A NIDILRR and VA TBI Model Systems Collaborative Project.

OBJECTIVE: To define and characterize extreme phenotypes based on perceived improvement in pain for persons with chronic pain following traumatic brain injury (TBI). SETTING: Eighteen Traumatic Brain Injury Model System (TBIMS) Centers. PARTICIPANTS: A total of 1762 TBIMS participants 1 to 30 years post-injury reporting chronic pain at their most recent follow-up interview. PRIMARY MEASURES: The Patient's Global Impression of Change (PGIC) related to pain treatment. Sociodemographic, injury, functional outcome, pain, and pain treatment characteristics. RESULTS: Participants were mostly male (73%), White (75%), middle-aged (mean 46 years), injured in motor vehicle accidents (53%), or falls (20%). Extreme phenotypes were created for an extreme improvement phenotype ( n = 512, 29.8%) defined as "moderately better" or above on the PGIC and an extreme no-change group ( n = 290, 16.9%) defined as no change or worse. Least absolute shrinkage and selection operator (LASSO) regression combined with logistic regression identified multivariable predictors of improvement versus no-change extreme phenotypes. Higher odds of extreme improvement phenotype were significantly associated with being female (odds ratio [OR] = 1.85), married versus single (OR = 2.02), better motor function (OR = 1.03), lower pain intensity (OR = 0.78), and less frequent pain, especially chest pain (OR = 0.36). Several pain treatments were associated with higher odds of being in the extreme improvement versus no-change phenotypes including pain medication (OR = 1.85), physical therapy (OR = 1.51), yoga (OR = 1.61), home exercise program (OR = 1.07), and massage (OR = 1.69). CONCLUSION: Investigation of extreme phenotypes based on perceived improvement with pain treatment highlights the ability to identify characteristics of individuals based on pain treatment responsiveness. A better understanding of the biopsychosocial characteristics of those who respond and do not respond to pain treatments received may help inform better surveillance, monitoring, and treatment. With further research, the identification of risk factors (such as pain intensity and frequency) for treatment response/nonresponse may provide indicators to prompt changes in care for individuals with chronic pain after TBI.

Hyperbaric hydrogen therapy improves secondary brain injury after head trauma.

Background: The pathophysiology of traumatic brain injury (TBI) is caused by the initial physical damage and by the subsequent biochemical damage (secondary brain injury). Oxidative stress is deeply involved in secondary brain injury, so molecular hydrogen therapy may be effective for TBI. Hydrogen gas shows the optimal effect at concentrations of 2% or higher, but can only be used up to 1.3% in the form of a gas cylinder mixed with oxygen gas, which may not be sufficiently effective. The partial pressure of hydrogen increases in proportion to the pressure, so hyperbaric hydrogen therapy (HBH2) is more effective than that at atmospheric pressure. Methods: A total of 120 mice were divided into three groups: TBI + non-treatment group (TBI group; n = 40), TBI + HBH2 group (n = 40), and non-TBI + non-treatment group (sham group; n = 40). The TBI and TBI + HBH2 groups were subjected to moderate cerebral contusion induced by controlled cortical impact. The TBI + HBH2 group received hyperbaric hydrogen therapy at 2 atmospheres for 90 minutes, at 30 minutes after TBI. Brain edema, neuronal cell loss in the injured hippocampus, neurological function, and cognitive function were evaluated. Results: The TBI + HBH2 group showed significantly less cerebral edema (p ≺ 0.05). Residual hippocampal neurons were significantly more numerous in the TBI + HBH2 group on day 28 (p ≺ 0.05). Neurological score and behavioral tests showed that the TBI + HBH2 group had significantly reduced hyperactivity on day 14 (p ≺ 0.01). Conclusion: Hyperbaric hydrogen therapy may be effective for posttraumatic secondary brain injury.

Investigation of Neuroprotective Effect of Shilajit Extract in Experimental Head Trauma Model Created in Rats.

AIM: To investigate the neuroprotective effect of shilajit extract in experimental head trauma. MATERIAL AND METHODS: Three groups of 33 Sprague Dawley Albino strain male rats were included in the study. Group 1 (n=11): trauma but not treated. Group 2 (n=11): trauma and treated with 0.5 mL / rat saline Group 3 (n=11): 150 mg / kg shilajit extract was administered intraperitoneally in the treatment of trauma. Following the head trauma, the indicated treatments were applied to the 2nd and 3rd groups at the first, twenty-four and forty-eighth hours. Brain tissues and blood samples were taken after the control animals were sacrificed at the 72nd hour in all groups after trauma. Sections prepared from cerebral cortex and ca1 region were examined with hematoxylin eosin and luxol fast blue staining. Total antioxidant capacity, total oxidant capacity and oxidative stress index were measured from blood samples taken after routine procedures. RESULTS: The number of red neurons and the severity of edema were significantly higher in both the cerebral cortex and the ca1 region in the group treated with trauma only and in the group administered saline after trauma compared to the group that received shilajit extract after trauma. The total antioxidant capacity increased significantly in blood samples taken only from the group treated with trauma and saline in post-trauma treatment compared to the group given post-traumatic shilajit extract, while shilajit extract given due to traumatic brain injury significantly decreased the total oxidant capacity and oxidative stress index values compared to the other groups. CONCLUSION: Shilajit extract has been shown to have a neuroprotective effect in the treatment of acute traumatic brain injury. Our study showed that shilajit may be a useful option in the treatment of secondary brain injury, in humans.

Tongqiao Huoxue Decoction ameliorates traumatic brain injury-induced gastrointestinal dysfunction by regulating CD36/15-LO/NR4A1 signaling, which fails when CD36 and CX3CR1 are deficient.

AIMS: Gastrointestinal (GI) dysfunction, as a common peripheral-organ complication after traumatic brain injury (TBI), is primarily characterized by gut inflammation and damage to the intestinal mucosal barrier (IMB). Previous studies have confirmed that TongQiao HuoXue Decoction (TQHXD) has strong anti-inflammatory properties and protects against gut injury. However, few have reported on the therapeutic effects of TQHXD in a TBI-induced GI dysfunction model. We aimed to explore the effects of TQHXD on TBI-induced GI dysfunction and the underlying mechanism thereof. METHODS: We assessed the protective effects and possible mechanism of TQHXD in treating TBI-induced GI dysfunction via gene engineering, histological staining, immunofluorescence (IF), 16S ribosomal ribonucleic acid (rRNA) sequencing, real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and flow cytometry (FCM). RESULTS: TQHXD administration ameliorated TBI-induced GI dysfunction by modulating the abundance and structure of bacteria; reconstructing the destroyed epithelial and chemical barriers of the IMB; and improving M1/M2 macrophage, T-regulatory cell (Treg)/T helper 1 cell (Th1 ), as well as Th17 /Treg ratios to preserve homeostasis of the intestinal immune barrier. Notably, Cluster of Differentiation 36 (CD36)/15-lipoxygenase (15-LO)/nuclear receptor subfamily 4 group A member 1 (NR4A1) signaling was markedly stimulated in colonic tissue of TQHXD-treated mice. However, insufficiency of both CD36 and (C-X3-C motif) chemokine receptor 1 (CX3CR1) worsened GI dysfunction induced by TBI, which could not be rescued by TQHXD. CONCLUSION: TQHXD exerted therapeutic effects on TBI-induced GI dysfunction by regulating the intestinal biological, chemical, epithelial, and immune barriers of the IMB, and this effect resulted from the stimulation of CD36/NR4A1/15-LO signaling; however, it could not do so when CX3CR1 and CD36 were deficient. TQHXD might therefore be a potential drug candidate for treating TBI-induced GI dysfunction.

A systematic review of heart rate variability (HRV) biofeedback treatment following traumatic brain injury (TBI).

OBJECTIVE: Autonomic nervous system dysregulation is a common consequence of traumatic brain injury (TBI). Heart rate variability (HRV) is a cost-effective measure of autonomic nervous system functioning, with studies suggesting decreased HRV following moderate-to-severe TBI. HRV biofeedback treatment may improve post-TBI autonomic nervous system functioning and post-injury emotional and cognitive functioning. We provide a systematic evidence-based review of the state of the literature and effectiveness of HRV biofeedback following TBI. METHOD: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two coders coded each article and provided quality ratings. Seven papers met inclusion criteria. All studies included a measure of emotional functioning and 5 studies (63%) included neuropsychological outcomes. RESULTS: Participants completed 11 sessions of HRV biofeedback on average (range = 1 to 40). HRV biofeedback was associated with improved HRV following TBI. There was a positive relationship between increased HRV and TBI recovery following biofeedback, including improvements in cognitive and emotional functioning, and physical symptoms such as headaches, dizziness, and sleep problems. CONCLUSION: The literature on HRV biofeedback for TBI is promising, but in its infancy; effectiveness is unclear due to poor-to-fair study quality, and potential publication bias (all studies reported positive results).

Neuroprotection and Therapeutic Implications of Creatine Supplementation for Brain Injury Complications.

Creatine supplementation has not been researched for Traumatic Brain Injury (TBI) extensively, but studies suggest potential as a neuroprotective agent and potential treatment for brain-injury complications. Patients suffering from TBI experience mitochondrial dysfunction, neuropsychological burden, and deficits in cognitive performance due to malperformance of brain creatine levels, diminished brain Adenosine Triphosphate (ATP) levels, glutamate toxicity, and oxidative stress. In this systemic review, the current available research is reviewed to examine the effects of creatine on common sequalae of TBI within children, adolescents, and mice. Past and present data still lacks the knowledge of creatine supplementation for the adult population and military members during TBI. PubMed was searched for studies which assessed the correlation between creatine supplementation of TBI complications. The search strategy yielded 40 results, of which 15 articles were included in this systemic review. The results of the review supported an apparent understanding creatine does offer an obvious benefit to patients suffering from TBI and post-injury complications under specific guidelines. Time and dose dependent metabolic alterations seem to be only exceptionally prevalent when given as a prophylaxis or if given acutely. Results are only clinically significant after a month of supplementation. Although patients may need many therapeutic treatments to recover from TBI, especially in acute resuscitation, creatine shows superior efficacy as a neuroprotective agent in battling the chronic manifestations which lead to oxidative stress and cognitive function post brain injury.

Acupuncture use for pain after traumatic brain injury: a NIDILRR Traumatic Brain Injury Model Systems cohort study.

BACKGROUND: Pain after traumatic brain injury (TBI) is common and can become chronic. Acupuncture is an increasingly popular non-pharmacologic option in the United States and is commonly used for pain. OBJECTIVE: We explored demographics, injury characteristics, and pain characteristics of individuals who reported using acupuncture for chronic pain after TBI. METHODS: We analyzed a subset of data collected as part of the Pain After Traumatic Brain Injury collaborative study and identified individuals reporting a history of acupuncture as part of management for chronic pain after TBI. We characterized and compared basic demographic data, pain treatment engagements, pain severity, pain interference, functional independence, and pain locations using descriptive and inferential statistics. RESULTS: Our sample included 1,064 individuals. Acupuncture use (n = 208) was lower proportionally among females, Blacks/African Americans, Asians, less educated, and nonmilitary service members. Insurance type varied between acupuncture and non-acupuncture users. Functional and pain outcomes were similar, but acupuncture users reported a higher number of pain sites. DISCUSSION: Acupuncture is one treatment utilized by individuals with TBI and chronic pain. Further investigation would be helpful to understand the barriers and facilitators of acupuncture use to inform clinical trials to examine the potential benefit of acupuncture on pain outcomes after TBI.

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.

Disparities in Chronic Pain Experience and Treatment History Among Persons With Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study.

OBJECTIVE: To determine disparities in pain severity, pain interference, and history of pain treatment for non-Hispanic Whites, non-Hispanic Blacks, and Hispanics with traumatic brain injury (TBI) and chronic pain. SETTING: Community following discharge from inpatient rehabilitation. PARTICIPANTS: A total of 621 individuals with medically documented moderate to severe TBI who had received acute trauma care and inpatient rehabilitation (440 non-Hispanic Whites, 111 non-Hispanic Blacks, and 70 Hispanics). DESIGN: A multicenter, cross-sectional, survey study. MAIN MEASURES: Brief Pain Inventory; receipt of opioid prescription; receipt of nonpharmacologic pain treatments; and receipt of comprehensive interdisciplinary pain rehabilitation. RESULTS: After controlling for relevant sociodemographic variables, non-Hispanic Blacks reported greater pain severity and greater pain interference relative to non-Hispanic Whites. Race/ethnicity interacted with age, such that the differences between Whites and Blacks were greater for older participants (for severity and interference) and for those with less than a high school education (for interference). There were no differences found between the racial/ethnic groups in the odds of having ever received pain treatment. CONCLUSIONS: Among individuals with TBI who report chronic pain, non-Hispanic Blacks may be more vulnerable to difficulties managing pain severity and to interference of pain in activities and mood. Systemic biases experienced by many Black individuals with regard to social determinants of health must be considered in a holistic approach to assessing and treating chronic pain in individuals with TBI.

Effects of Self-Administered Acupressure on Fatigue Following Traumatic Brain Injury: A Randomized Controlled Trial.

BACKGROUND: Fatigue is a common symptom after a traumatic brain injury (TBI) and may persist for weeks or years. However, nonpharmacological management strategies for fatigue alleviations are almost nonexistent; thus, effective fatigue management programs are needed urgently. PURPOSES: We aimed to evaluate the effects of self-administered acupressure programs on post-TBI fatigue and heart rate variability and identify the possible correlation between the improvements in fatigue symptoms and the changes in heart rate variability. DESIGN: This randomized controlled trial included 2-point acupressure (TPA; n = 27), 5-point acupressure (FPA; n = 27), and usual care (UC, control; n = 27) groups who underwent several assessments before and after the study intervention. Heart rate variability was evaluated at baseline, weeks 2 and 3, and treatment completion. METHODS: The TPA and FPA groups self-administered acupressure (3 minutes per acupoint; bilateral), thrice daily for 4 weeks, whereas the UC group received routine treatment without acupressure. RESULTS: Both the TPA and FPA groups exhibited substantial improvements in fatigue symptoms compared with the baseline findings in the UC group. In addition, the TPA and FPA groups exhibited increased high-frequency power and mean number of times per hour in which the changes in successive normal sinus intervals (RR) gradually exceeded 50 ms (pNN50). Changes in high-frequency power and pNN50 were correlated with improvements in post-TBI fatigue symptoms. CONCLUSION: Acupressure may alleviate chronic fatigue and enhance parasympathetic activity in TBI survivors. The enhancement of parasympathetic activity may be correlated with improvements in post-TBI fatigue symptoms. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers should incorporate self-administered acupressure into the care plans for TBI survivors to improve their fatigue symptoms.

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.

Broad Therapeutic Time Window for Driving Motor Recovery After TBI Using Activity-Dependent Stimulation.

BACKGROUND: After an acquired injury to the motor cortex, the ability to generate skilled movements is impaired, leading to long-term motor impairment and disability. While rehabilitative therapy can improve outcomes in some individuals, there are no treatments currently available that are able to fully restore lost function. OBJECTIVE: We previously used activity-dependent stimulation (ADS), initiated immediately after an injury, to drive motor recovery. The objective of this study was to determine if delayed application of ADS would still lead to recovery and if the recovery would persist after treatment was stopped. METHODS: Rats received a controlled cortical impact over primary motor cortex, microelectrode arrays were implanted in ipsilesional premotor and somatosensory areas, and a custom brain-machine interface was attached to perform the ADS. Stimulation was initiated either 1, 2, or 3 weeks after injury and delivered constantly over a 4-week period. An additional group was monitored for 8 weeks after terminating ADS to assess persistence of effect. Results were compared to rats receiving no stimulation. RESULTS: ADS was delayed up to 3 weeks from injury onset and still resulted in significant motor recovery, with maximal recovery occurring in the 1-week delay group. The improvements in motor performance persisted for at least 8 weeks following the end of treatment. CONCLUSIONS: ADS is an effective method to treat motor impairments following acquired brain injury in rats. This study demonstrates the clinical relevance of this technique as it could be initiated in the post-acute period and could be explanted/ceased once recovery has occurred.

A Systematic Review on Traumatic Brain Injury Pathophysiology and Role of Herbal Medicines in its Management.

BACKGROUND: Traumatic brain injury (TBI) is a worldwide problem. Almost about sixtynine million people sustain TBI each year all over the world. Repetitive TBI linked with increased risk of neurodegenerative disorder such as Parkinson, Alzheimer, traumatic encephalopathy. TBI is characterized by primary and secondary injury and exerts a severe impact on cognitive, behavioral, psychological and other health problem. There were various proposed mechanism to understand complex pathophysiology of TBI but still there is a need to explore more about TBI pathophysiology. There are drugs present for the treatment of TBI in the market but there is still need of more drugs to develop for better and effective treatment of TBI, because no single drug is available which reduces the further progression of this injury. OBJECTIVE: The main aim and objective of structuring this manuscript is to design, develop and gather detailed data regarding about the pathophysiology of TBI and role of medicinal plants in its treatment. METHOD: This study is a systematic review conducted between January 1995 to June 2021 in which a consultation of scientific articles from indexed periodicals was carried out in Science Direct, United States National Library of Medicine (Pubmed), Google Scholar, Elsvier, Springer and Bentham. RESULTS: A total of 54 studies were analyzed, on the basis of literature survey in the research area of TBI. CONCLUSION: Recent studies have shown the potential of medicinal plants and their chemical constituents against TBI therefore, this review targets the detailed information about the pathophysiology of TBI and role of medicinal plants in its treatment.

The Utility of Melatonin for the Treatment of Sleep Disturbance After Traumatic Brain Injury: A Scoping Review.

OBJECTIVE: To investigate the utility of melatonin supplementation as a treatment option for individuals with sleep disturbance after traumatic brain injury (TBI). DATA SOURCES: A systematic search was conducted in 6 electronic databases (Medline, AMED, CINAHL, Embase, Scopus, and SPORTDiscus) from earliest records to April 2022. STUDY SELECTION: Studies were eligible for inclusion if they met the following criteria: a) human participants with sleep disturbance after TBI, b) melatonin or melatonergic agent used as an intervention to treat sleep disturbance, and c) outcomes of melatonin administration reported. All TBI severity types (mild, moderate, and severe) were eligible. The initial search retrieved a total of 595 articles, with 9 studies meeting the eligibility criteria. DATA EXTRACTION: Two reviewers independently extracted data from eligible studies and assessed methodological quality. Extracted data consisted of participant and injury characteristics, melatonin interventional properties, and sleep outcome. Methodological quality was assessed via the Downs and Black checklist. DATA SYNTHESIS: A total of 251 participants with TBI-induced sleep disturbance (mean age range: 14.0-42.5 years) were included. Melatonin, Circadin (prolonged-release melatonin), or Ramelteon (melatonin receptor agonist) were administered. Dosages and intervention duration ranged from 2 to 10 mg and 3 to 12 weeks, respectively. Eight out of 9 studies reported positive outcomes after melatonin treatment. Significant improvements in subjective sleep quality, objective sleep efficiency, and total sleep time were found with melatonin. Reductions in self-reported fatigue, anxiety, and depressive symptoms were also observed with melatonin treatment. No serious adverse events were reported after melatonin administration. CONCLUSION: Melatonin has good tolerability after short-term use and the potential to be a therapeutic agent for those with sleep disturbance after TBI. Melatonin was shown to be beneficial to sleep quality, sleep duration, and sleep efficiency. Additional clinically relevant outcomes of improved mental health suggest that melatonin use may be a promising treatment option for individuals experiencing co-occurring disorders of mood and sleep disturbance post-injury.

Hyperbaric oxygen therapy for cognitive impairments in patients with traumatic brain injury: A systematic review.

Cognitive deficits are the most common impairments after traumatic brain injury (TBI). It can be linked with poor physical function. Hyperbaric oxygen therapy (HBOT) increases blood flow and oxygen supply to the brain. This review aimed to summarize and evaluate the available literature on the influences of HBOT on cognitive deficits in patients with TBI. PubMed, SCOPUS, PEDro, REHABDATA, MIDLINE, CHINAL, EMBASE, and Web of Science were searched from inception until June 2021. The methodological quality was measured using the physiotherapy evidence database (PEDro) scale. Ten studies met the eligibility criteria. Six studies were randomized controlled trials, and four were pilot studies. The scores on the PEDro scale ranged from two to nine, with a median score of seven. The included studies showed heterogeneity results for the beneficial effects of HBOT on improving cognitive functions in patients with TBI. The evidence for the beneficial effects of HBOT on cognitive functions post-TBI was limited. Further randomized controlled trials with large sample sizes are strongly needed to understand the effects of HBOT on cognitive functions in patients with TBI.

Saffron Extract Attenuates Anxiogenic Effect and Improves Cognitive Behavior in an Adult Zebrafish Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) has the highest mortality rates worldwide, yet effective treatment remains unavailable. TBI causes inflammatory responses, endoplasmic reticulum stress, disruption of the blood-brain barrier and neurodegeneration that lead to loss of cognition, memory and motor skills. Saffron (Crocus sativus L.) is known for its anti-inflammatory and neuroprotective effects, which makes it a potential candidate for TBI treatment. Zebrafish (Danio rerio) shares a high degree of genetic homology and cell signaling pathways with mammals. Its active neuro-regenerative function makes it an excellent model organism for TBI therapeutic drug identification. The objective of this study was to assess the effect of saffron administration to a TBI zebrafish model by investigating behavioral outcomes such as anxiety, fear and memory skills using a series of behavioral tests. Saffron exhibited anxiolytic effect on anxiety-like behaviors, and showed prevention of fear inhibition observed after TBI. It improved learning and enhanced memory performance. These results suggest that saffron could be a novel therapeutic enhancer for neural repair and regeneration of networks post-TBI.

Animal-Assisted Therapy for Patients With Disorders of Consciousness Following a Traumatic Brain Injury (June 2013-October 2020).

Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each Systematic Review Brief summarizes the evidence on a theme related to a systematic review topic. This Systematic Review Brief presents findings from the systematic review on the effectiveness of animal-assisted therapy to improve arousal and awareness for people with disorders of consciousness following a traumatic brain injury.