Function In Traumatic Brain Injury Research Articles

Efficacy of high-dose versus low-dose vitamin D supplementation on serum levels of inflammatory factors and mortality rate in severe traumatic brain injury patients: study protocol for a randomized placebo-controlled trial

BackgroundTraumatic brain injury (TBI) is the most common trauma worldwide and is a leading cause of injury-related death and disability. Inflammation is initiated as a result of the TBI, which is in association with severity of illness and mortality in brain trauma patients, especially in subdural hemorrhage and epidural hemorrhage cases. A high percentage of adults admitted to the intensive care unit with TBI are diagnosed with vitamin D deficiency; this deficiency may induce impaired immune responses and increase the risk of infections. Vitamin D intervention has been shown to modulate pro- and anti-inflammatory cytokines in non-critically ill patients, but to date, there is no substantial data on the effectiveness of vitamin D for the improvement of immune function in traumatic brain injury patients.Methods/designA randomized clinical trial (RCT) will be performed on 74 Iranian adults 18–65 years old with brain trauma and will be treated daily with vitamin D supplements (100,000 IU oral drop) or a similar placebo (1000 IU) for 5 days.DiscussionIf this randomized clinical trial demonstrates reductions in inflammatory cytokines, it would provide evidence for a multicenter clinical trial to evaluate the efficacy of vitamin D supplementation in neurocritically ill patients. Since vitamin D supplements are inexpensive and safe, this clinical trial could have the potential to improve clinical outcomes in traumatic brain injury patients through reduction of inflammation and infection-associated morbidity and mortality rates.Trial registrationIranian Registry of Clinical Trials, IRCT20180619040151N3. Registered on 10 August 2019.

Memory Disorders as a Function of Traumatic Brain Injury. Word Completion, Recall of Words and Actions

The memory performance of a group with traumatic brain injury and a matched control group was assessed using the following methods (a) word completion, (b) immediate free, final free and final cued recall of words and (c) immediate free and final free recall of subject-performed tasks (SPTs) and SPTs without motor action (SPTs-WA). The brain-injured (BI) group was significantly inferior relative to the control group in all recall tests except immediate free recall of words. No difference was revealed in the word completion test. The BI-group benefitted less by cues presented either at retrieval (final cued recall of words) or at the time of encoding already built-in in the stimulus (SPTs and SPTs-WA). The results were discussed in terms of the neuropathological background of the patients in the BI-group suggesting that frontal dysfunction could play a critical role. When comparing the tests within the BI-group, however, the performance was better when cues were present and especially so for long-term memory. Motor activity also facilitated long-term memory. Finally, an attempt was made to specify conditions for guidance in the construction of training programmes.

Effects of advanced age upon astrocyte-specific responses to acute traumatic brain injury in mice

BackgroundOlder-age individuals are at the highest risk for disability from a traumatic brain injury (TBI). Astrocytes are the most numerous glia in the brain, necessary for brain function, yet there is little known about unique responses of astrocytes in the aged-brain following TBI.MethodsOur approach examined astrocytes in young adult, 4-month-old, versus aged, 18-month-old mice, at 1, 3, and 7 days post-TBI. We selected these time points to span the critical period in the transition from acute injury to presumably irreversible tissue damage and disability. Two approaches were used to define the astrocyte contribution to TBI by age interaction: (1) tissue histology and morphological phenotyping, and (2) transcriptomics on enriched astrocytes from the injured brain.ResultsAging was found to have a profound effect on the TBI-induced loss of astrocyte function needed for maintaining water transport and edema—namely, aquaporin-4. The aged brain also demonstrated a progressive exacerbation of astrogliosis as a function of time after injury. Moreover, clasmatodendrosis, an underrecognized astrogliopathy, was found to be significantly increased in the aged brain, but not in the young brain. As a function of TBI, we observed a transitory refraction in the number of these astrocytes, which rebounded by 7 days post-injury in the aged brain. Transcriptomic data demonstrated disproportionate changes in genes attributed to reactive astrocytes, inflammatory response, complement pathway, and synaptic support in aged mice following TBI compared to young mice. Additionally, our data highlight that TBI did not evoke a clear alignment with the previously defined “A1/A2” dichotomy of reactive astrogliosis.ConclusionsOverall, our findings point toward a progressive phenotype of aged astrocytes following TBI that we hypothesize to be maladaptive, shedding new insights into potentially modifiable astrocyte-specific mechanisms that may underlie increased fragility of the aged brain to trauma.

MicroRNA‐9‐5p alleviates blood–brain barrier damage and neuroinflammation after traumatic brain injury

The level of microRNA‐9‐5p (miRNA‐9‐5p) in brain tissues is significantly changed after traumatic brain injury (TBI). However, the effect of miRNA‐9‐5p for brain function in TBI has not been elucidated. In this study, a controlled cortical impact model was used to induce TBI in Sprague–Dawley rats, and an oxygen glucose deprivation model was used to mimic the pathological state in vitro. Brain microvascular endothelial cells (BMECs) and astrocytes were extracted from immature Sprague–Dawley rats and cocultured to reconstruct blood–brain barrier (BBB) in vitro. The results show that the level of miRNA‐9‐5p was significantly increased in brain tissues after TBI, and up‐regulation of miRNA9‐5p contributed to the recovery of neurological function. Up‐regulation of miRNA‐9‐5p with miRNA agomir may significantly alleviate apoptosis, neuroinflammation, and BBB damage in rats after TBI. Moreover, a dual luciferase reporter assay confirmed that miRNA‐9‐5p is a post‐transcriptional modulator of Ptch‐1. In in vitro experiments, the results confirmed that up‐regulation of miRNA‐9‐5p with miRNA mimic alleviates cellular apoptosis, inflammatory response, and BBB damage mainly by inhibiting Ptch‐1. In addition, we found that the activation of Hedgehog pathway was accompanied by inhibition of NF‐κB/MMP‐9 pathway in the BMECs treated with miRNA‐9‐5p mimic. Taken together, these results indicate that up‐regulation of miRNA‐9‐5p alleviates BBB damage and neuroinflammatory responses by activating the Hedgehog pathway and inhibiting NF‐κB/MMP‐9 pathway, which promotes the recovery of neurological function after TBI.

Music Therapy Enhances Executive Functions and Prefrontal Structural Neuroplasticity after Traumatic Brain Injury: Evidence from a Randomized Controlled Trial.

Traumatic brain injury (TBI) causes lifelong cognitive deficits, particularly impairments of executive functioning (EF). Musical training and music-based rehabilitation have been shown to enhance cognitive functioning and neuroplasticity, but the potential rehabilitative effects of music in TBI are still largely unknown. The aim of the present crossover randomized controlled trial (RCT) was to determine the clinical efficacy of music therapy on cognitive functioning in TBI and to explore its neural basis. Using an AB/BA design, 40 patients with moderate or severe TBI were randomized to receive a 3-month neurological music therapy intervention either during the first (AB, n = 20) or second (BA, n = 20) half of a 6-month follow-up period. Neuropsychological and motor testing and magnetic resonance imaging (MRI) were performed at baseline and at the 3-month and 6-month stage. Thirty-nine subjects who participated in baseline measurement were included in an intention-to-treat analysis using multiple imputation. Results showed that general EF (as indicated by the Frontal Assessment Battery [FAB]) and set shifting improved more in the AB group than in the BA group over the first 3-month period and the effect on general EF was maintained in the 6-month follow-up. Voxel-based morphometry (VBM) analysis of the structural MRI data indicated that gray matter volume (GMV) in the right inferior frontal gyrus (IFG) increased significantly in both groups during the intervention versus control period, which also correlated with cognitive improvement in set shifting. These findings suggest that neurological music therapy enhances EF and induces fine-grained neuroanatomical changes in prefrontal areas.

STUDY OF CEREBROPROTECTIVE EFFICIENCY OF ADEMOL AND MAGNESIUM SULPHATE IN EXPERIMENTAL MODEL OF THE TRAUMATIC BRAIN INJURY

Objective - сompare the effectiveness of adamantane derivative 1-adamantyletylox-3-morpholino-2-propanol hydrochloride (Ademol) and magnesium sulfate for the correction of mystic function and neurological deficit in a rat model of traumatic braininjury.Material and methods. The therapeutic effect of Ademol on simulated traumatic braininjury was assessed using doses of 1, 2 and 4 mg/kg. Pseudo-operated animals received a0,9% solution of NaCl at the rate of up to the volume of the most effective dose of Ademol.As a drug for the control group, 0,9% NaCl solution was used at a dose of 2 ml/kgintravenous in the same regimen. Neurological deficit in rats with traumatic brain injurywas assessed on the first day and at the end of the acute period (on the eighth day) usingthe stroke-index C.P. McGrow. The ability of animals to learn and memorize an aversivestimulus was investigated in a passive avoidance conditional response test. Thetechnique is based on the innate instinct of rats to a limited darkened space. Preservation of the conditioned reaction was checked after 24 hours by the change in thelatent time of entry of the rat into the dark compartment. Also noted The number ofanimals that tried to enter the dark chamber, but did not complete the attempt was alsonoted.Results. Investigating the effect of course therapy with Ademol solution on the degree ofneurological deficit reduction, it can be noted that this property of the studied drug wasdominated by magnesium sulfate solution in the first day of application 24% and on theeighth day 30% (p <0,05). In restoring mental functions in traumatic brain injury, eightday rat therapy with magnesium sulphate solution somewhat improved memory, but wasinferior in performance to Ademol, which approached the test results of the passiveavoidance conditional test to the results of pseudo-operated animals.Conclusion. The results, obtained for the correction of neurological deficit, make itpossible to assert that there is no reliable efficacy of using magnesium sulfate inexperimental traumatic brain injury in rats. Ademol, in contrast to magnesium sulfatesolution, contributed to a reduction in the severity of neurological disorders, which wasaccompanied by an improvement in the mental functions in animals on the eighth day oftraumatic brain injury.

Default Mode Network Connectivity Predicts Emotion Recognition and Social Integration After Traumatic Brain Injury

Moderate-severe traumatic brain injury (TBI) may result in difficulty with emotion recognition, which has negative implications for social functioning. As aspects of social cognition have been linked to resting-state functional connectivity (RSFC) in the default mode network (DMN), we sought to determine whether DMN connectivity strength predicts emotion recognition and level of social integration in TBI. To this end, we examined emotion recognition ability of 21 individuals with TBI and 27 healthy controls in relation to RSFC between DMN regions. Across all participants, decreased emotion recognition ability was related to increased connectivity between dorsomedial prefrontal cortex (dmPFC) and temporal regions (temporal pole and parahippocampal gyrus). Furthermore, within the TBI group, connectivity between dmPFC and parahippocampal gyrus predicted level of social integration on the Community Integration Questionnaire, an important index of post-injury social functioning in TBI. This finding was not explained by emotion recognition ability, indicating that DMN connectivity predicts social functioning independent of emotion recognition. These results advance our understanding of the neural underpinnings of emotional and social processes in both healthy and injured brains, and suggest that RSFC may be an important marker of social outcomes in individuals with TBI.

Traumatic Brain Injury-related voiding dysfunction in mice is caused by damage to rostral pathways, altering inputs to the reflex pathways

Brain degeneration, including that caused by traumatic brain injury (TBI) often leads to severe bladder dysfunction, including incontinence and lower urinary tract symptoms; with the causes remaining unknown. Male C57BL/6J mice underwent repetitive moderate brain injury (rmdTBI) or sham injury, then mice received either cis P-tau monoclonal antibody (cis mAb), which prevents brain degeneration in TBI mice, or control (IgG). Void spot assays revealed age-dependent incontinence in IgG controls 8 months after injury, while cis mAb treated or sham mice showed no dysfunction. No obvious bladder pathology occurred in any group. Urodynamic cystometry in conscious mice revealed overactive bladder, reduced maximal voiding pressures and incontinence in IgG control, but not sham or cis mAb treated mice. Hyperphosphorylated tau deposition and neural tangle-like pathology occurred in cortical and hippocampal regions only of IgG control mice accompanied with post-traumatic neuroinflammation and was not seen in midbrain and hindbrain regions associated with bladder filling and voiding reflex arcs. In this model of brain degeneration bladder dysfunction results from rostral, and not hindbrain damage, indicating that rostral brain inputs are required for normal bladder functioning. Detailed analysis of the functioning of neural circuits controlling bladder function in TBI should lead to insights into how brain degeneration leads to bladder dysfunction, as well as novel strategies to treat these disorders.

Effects of transection of cervical sympathetic trunk on cognitive function of traumatic brain injury rats.

Objective: To observe the effects of transection of cervical sympathetic trunk (TCST) on the cognitive function of traumatic brain injury (TBI) rats and the potential mechanisms.Methods: A total of 288 adult male SD rats were divided into 3 groups using a random number table: TBI group (n=96), TBI + TCST group (n=96) and Sham group (n=96). The water maze test was performed before TBI (T0) and at day 1 (T1), day 2 (T2), day 3 (T3), 1 week (T4), 2 weeks (T5), 6 weeks (T6) and 12 weeks (T7) after TBI. The levels of α1-adrenergic receptors (α1-ARs), α2-adrenergic receptors (α2-ARs), toll-like receptor 4 (TLR-4) and P38 in hippocampi were detected by real-time PCR. Hippocampal P38 expression was assayed by Western blot. The expressions of interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and brain-derived neurotrophic factor (BDNF) were examined by immunohistochemistry. Noradrenaline (NE) expression in plasma was evaluated by ELISA. The respiratory control ratio (RCR) of brain mitochondria was detected using a Clark oxygen electrode.Results: TCST effectively improved the cognitive function of TBI rats. TCST significantly inhibited sympathetic activity in the rats and effectively inhibited inflammatory responses. The expression of BDNF at T1-T6 in TBI+TCST group was higher than that in TBI group (P<0.05). Furthermore, P38 expression was inhibited more effectively in TBI+TCST group (P<0.05), than in TBI group (P<0.05), and the RCR of the brain was significantly higher in TBI+TCST group than in TBI group (P<0.05).Conclusions: TCST can enhance cognitive function in TBI rats by inhibiting sympathetic activity, reducing inflammatory responses and brain edema, upregulating BDNF and improving brain mitochondrial function.

Effect of silencing aquaporin 4 on learning and memory dysfunction in rats with traumatic brain injury

To observe the protein expression related to cognitive and learning memory function, and to investigate the effect of aquaporin 4 (AQP4) silence on learning and memory function in traumatic brain injury (TBI) rats. Ninety-six healthy adult male Wistar rats were divided into groups according to the random number table. (1) Forty-eight rats were divided into sham operation (sham) group, TBI group (by using modified Feeney method), AQP4 RNA interference (RNAi) negative group [TBI+meaningless small interfering RNA (siRNA)-AQP4 liposome solution 10 μL], and AQP4 RNAi group (TBI+siRNA-AQP4 liposome solution 10 μL). In each group, brain tissues of 4 rats were harvested at 1, 6 and 12 hours respectively. The protein expressions of hippocampus AQP4, general control nonderepressible 2 kinase (GCN2), cyclic adenosine monophosphate response element binding protein (CREB) and phosphorylated CREB (p-CREB) were detected by Western Blot. (2) In addition, 48 rats were divided into normal control group (control group), sham group, TBI group and AQP4 RNAi group, brain water content were measured in 6 of them after 12 hours of injury, and 6 were used in Morris water maze test. (1) The protein expressions of hippocampus AQP4 and GCN2 in TBI group were significantly higher than those in sham group, and increased gradually with time with statistical difference at 12 hours (AQP4 protein: 5.03±0.09 vs. 1, GCN2 protein: 4.01±0.13 vs. 1, both P < 0.01); the protein expressions of hippocampus CREB and p-CREB were significantly lower than those in sham group, and decreased gradually with time with statistical difference at 12 hours (CREB protein: 0.38±0.03 vs. 1, p-CREB protein: 0.38±0.03 vs. 1, both P < 0.01). Compared with TBI group, the protein expressions of AQP4 in AQP4 RNAi group was significantly decreased (1 hour: 1.02±0.04 vs. 2.23±0.05, 6 hours: 1.23±0.03 vs. 2.59±0.04, 12 hours: 2.20±0.08 vs. 5.03±0.09, all P < 0.01), but there were no significant difference in the expressions of GCN2, CREB or p-CREB. There was no significant difference in the expression of protein between AQP4 RNAi negative group and TBI group. (2) The brain water content in TBI group was significantly higher than that in control group and sham group [(83.7±0.4)% vs. (76.2±0.2)%, (76.2±0.3)%, both P < 0.01]. The brain water content in AQP4 RNAi group [(78.8±0.3)%] was significantly decreased as compared with that in TBI group (P < 0.01). The latency of Morris water maze test was significantly prolonged in the day 11, 13 and 15 after the injury of the TBI group and AQP4 RNAi group, and the exploration time was significantly shortened. Compared with TBI group, the incubation period of AQP4 RNAi group was significantly shortened at 15 days (s: 60.2±11.1 vs. 62.0±11.5, P < 0.05), and the exploration time was significantly prolonged (s: 37.0±8.5 vs. 32.7±9.2, P < 0.05). The impairment of cognitive and learning memory function in rats after TBI was significantly related to the changes in CREB and GCN2 in cognitive and learning memory function. After RNAi treatment, the cognitive and learning and memory function of rats was not improved obviously, but the brain edema could be alleviated.

Assessment of Platelet Function in Traumatic Brain Injury-A Retrospective Observational Study in the Neuro-Critical Care Setting.

Despite seemingly functional coagulation, hemorrhagic lesion progression is a common and devastating condition following traumatic brain injury (TBI), stressing the need for new diagnostic techniques. Multiple electrode aggregometry (MEA) measures platelet function and could aid in coagulopathy assessment following TBI. The aims of this study were to evaluate MEA temporal dynamics, influence of concomitant therapy, and its capabilities to predict lesion progression and clinical outcome in a TBI cohort. Adult TBI patients in a neurointensive care unit that underwent MEA sampling were retrospectively included. MEA was sampled if the patient was treated with antiplatelet therapy, bled heavily during surgery, or had abnormal baseline coagulation values. We assessed platelet activation pathways involving the arachidonic acid receptor (ASPI), P2Y12 receptor, and thrombin receptor (TRAP). ASPI was the primary focus of analysis. If several samples were obtained, they were included. Retrospective data were extracted from hospital charts. Outcome variables were radiologic hemorrhagic progression and Glasgow Outcome Scale assessed prospectively at 12 months posttrauma. MEA levels were compared between patients on antiplatelet therapy. Linear mixed effect models and uni-/multivariable regression models were used to study longitudinal dynamics, hemorrhagic progression and outcome, respectively. In total, 178 patients were included (48% unfavorable outcome). ASPI levels increased from initially low values in a time-dependent fashion (p < 0.001). Patients on cyclooxygenase inhibitors demonstrated low ASPI levels (p < 0.001), while platelet transfusion increased them (p < 0.001). The first ASPI (p = 0.039) and TRAP (p = 0.009) were significant predictors of outcome, but not lesion progression, in univariate analyses. In multivariable analysis, MEA values were not independently correlated with outcome. A general longitudinal trend of MEA is identified in this TBI cohort, even in patients without known antiplatelet therapies. Values appear also affected by platelet inhibitory treatment and by platelet transfusions. While significant in univariate models to predict outcome, MEA values did not independently correlate to outcome or lesion progression in multivariable analyses. Further prospective studies to monitor coagulation in TBI patients are warranted, in particular the interpretation of pathological MEA values in patients without antiplatelet therapies.

Traumatic Brain Injury-3Performance-Based Assessment of Executive Functioning in Traumatic Brain Injury

Traumatic Brain Injury-3Performance-Based Assessment of Executive Functioning in Traumatic Brain Injury

Modification of ubiquitin C-terminal hydrolase L1 by reactive lipid species: role in neural regeneration and diseases of aging.

Modification of ubiquitin C-terminal hydrolase L1 by reactive lipid species: role in neural regeneration and diseases of aging.

Executive Functioning in Traumatic Brain Injury: A Detailed Investigation of the Hayling Test

Executive Functioning in Traumatic Brain Injury: A Detailed Investigation of the Hayling Test

Pragmatic communication disorders and cognitive functions in traumatic brain injury

Pragmatic communication disorders and cognitive functions in traumatic brain injury

Essential Roles of Neutral Ceramidase and Sphingosine in Mitochondrial Dysfunction Due to Traumatic Brain Injury

In addition to immediate brain damage, traumatic brain injury (TBI) initiates a cascade of pathophysiological events producing secondary injury. The biochemical and cellular mechanisms that comprise secondary injury are not entirely understood. Herein, we report a substantial deregulation of cerebral sphingolipid metabolism in a mouse model of TBI. Sphingolipid profile analysis demonstrated increases in sphingomyelin species and sphingosine concurrently with up-regulation of intermediates of de novo sphingolipid biosynthesis in the brain. Investigation of intracellular sites of sphingosine accumulation revealed an elevation of sphingosine in mitochondria due to the activation of neutral ceramidase (NCDase) and the reduced activity of sphingosine kinase 2 (SphK2). The lack of change in gene expression suggested that post-translational mechanisms are responsible for the shift in the activities of both enzymes. Immunoprecipitation studies revealed that SphK2 is complexed with NCDase and cytochrome oxidase (COX) subunit 1 in mitochondria and that brain injury hindered SphK2 association with the complex. Functional studies showed that sphingosine accumulation resulted in a decreased activity of COX, a rate-limiting enzyme of the mitochondrial electron transport chain. Knocking down NCDase reduced sphingosine accumulation in mitochondria and preserved COX activity after the brain injury. Also, NCDase knockdown improved brain function recovery and lessened brain contusion volume after trauma. These studies highlight a novel mechanism of secondary TBI involving a disturbance of sphingolipid-metabolizing enzymes in mitochondria and suggest a critical role for mitochondrial sphingosine in promoting brain injury after trauma.

Cerebral Blood Flow and Apoptosis-Associated Factor with Electroacupuncture in a Traumatic Brain Injury Rat Model

Electroacupuncture (EA) has been widely used for treatment of stroke, but there is little information on the effect of EA on the neuroprotective function in traumatic brain injury (TBI). The aim of the present study was to investigate the protective effects and mechanisms of EA treatment in a TBI rat model. Male Sprague-Dawley rats were randomly divided into four groups: sham operation, TBI control, TBI+EA treated for 30 min or TBI+EA treated for 60 min. The animals were treated with EA immediately after TBI. The EA was applied at acupuncture points GV20, GV26, LI4 and KI1 with a dense-dispersed wave, frequencies of 0.2 and 1 Hz, and amplitude of 1 mA for 30 or 60 min. Regional blood flow, cell infarction volume, extent of neuronal apoptosis, expression of cell apoptosis-associated factor transforming growth-interacting factor (TGIF) were studied, and functional outcome was assessed by running speed test. All tests except regional blood flow were performed 72 h after TBI onset. Immediately after TBI, compared with the TBI control groups, the regional blood flow was significantly increased by EA treatment for 60 min. Compared with the TBI controls 72 h after TBI, the TBI-induced run speed impairment, infarction volume, neuronal apoptosis and apoptosis-associated TGIF expression were significantly improved by EA treatment. The treatment of TBI in the acute stage with EA for 60 min could increase the regional blood flow and attenuate the levels of TGIF in the injured cortex, might lead to a decrease in neuronal apoptosis and cell infarction volume, and might represent one mechanism by which functional recovery may occur.

Assessing Frontal Behavioral Syndromes and Cognitive Functions in Traumatic Brain Injury

This study examined the relationship between individual and family ratings on a measure of frontal behaviors using the Frontal Systems Behavior Scale (FrSBe). Additionally, this study investigated whether self-reported symptoms of frontal-lobe dysfunction correspond to neuropsychological performance, particularly those tests measuring executive functions. Thirty-three individuals with moderate-to-severe traumatic brain injury (TBI) and 19 healthy individuals completed the FrSBe and neuropsychological measures. Results indicated that the self-ratings of individuals’ apathy, disinhibition, and executive dysfunction significantly increased from before to after injury, as did the family members’ ratings, with no significant difference between the patients’ and family members’ reports for any of the three FrSBe subscales. Although individuals with TBI demonstrated impairments in neuropsychological measures, including measures of executive functioning, few significant correlations were found between the patients’ FrSBe ratings and measures of cognitive functioning. This suggests that information from the FrSBe may differ from information gathered during a cognitive evaluation and may enhance our understanding of the behavioral sequelae following TBI that may not be captured by neuropsychological assessment alone.

Enzogenol for cognitive functioning in traumatic brain injury: a pilot placebo‐controlled RCT

Enzogenol, a flavonoid-rich extract from Pinus radiata bark with antioxidant and anti-inflammatory properties has been shown to improve working memory in healthy adults. In traumatic brain injury (TBI), oxidation and inflammation have been linked to poorer cognitive outcomes. Hence, this phase II, randomized controlled trial investigated safety, compliance and efficacy of Enzogenol for improving cognitive functioning in people following mild TBI. Sixty adults, who sustained a mild TBI, 3-12 months prior to recruitment, and who were experiencing persistent cognitive difficulties [Cognitive Failures Questionnaire (CFQ) score > 38], were randomized to receive Enzogenol (1000 mg/day) or matching placebo for 6 weeks. Subsequently, all participants received Enzogenol for a further 6 weeks, followed by placebo for 4 weeks. Compliance, side-effects, cognitive failures, working and episodic memory, post-concussive symptoms and mood were assessed at baseline, 6, 12 and 16 weeks. Simultaneous estimation of treatment effect and breakpoint was effected, with confidence intervals (CIs) obtained through a treatment-placebo balance-preserving bootstrap procedure. Enzogenol was found to be safe and well tolerated. Trend and breakpoint analyses showed a significant reduction in cognitive failures after 6 weeks [mean CFQ score, 95% CI, Enzogenol versus placebo -6.9 (-10.8 to -4.1)]. Improvements in the frequency of self-reported cognitive failures were estimated to continue until week 11 before stabilizing. Other outcome measures showed some positive trends but no significant treatment effects. Enzogenol supplementation is safe and well tolerated in people after mild TBI, and may improve cognitive functioning in this patient population. This study provides Class IIB evidence that Enzogenol is well tolerated and may reduce self-perceived cognitive failures in patients 3-12 months post-mild TBI.

Neuropsychological assessment of executive functions in traumatic brain injury: Hot and cold components.

present study compared decision-making processing between patients with traumatic brain injury (TBI) and healthy controls. The study also sought to identify dissociations in the frequency of deficits in executive functions (EF) tasks that mainly assess decision making (DM; hot component) and inhibition (cold component) following TBI. The sample was composed of 16 post- TBI adults aged between 18 and 68 years and 16 healthy controls matched by age and education. Decision-making was assessed with the Iowa Gambling Task (IGT), and inhibitory control was assessed with the Trail Making Task (TMT) and Hayling Test. No differences were found between groups in total scores and block scores on the IGT. However, TBI patients preferred the disadvantageous decks, with no evidence of learning during the task. Seven patients presented dissociations between deficient DM on the IGT and accurate inhibition on the Hayling Test and TMT. Conversely, five patients presented partial dissociations between deficits in the IGT and TMT and opposite performance in the Hayling Test. Only three patients exhibited deficits on all of the instruments. These results indicate that patients can maintain comparable performance on the IGT after TBI. Therefore we found dissociations in hot and cold executive components.