Onset Of Traumatic Brain Injury Research Articles

The economic impact of cannabis use disorder and dementia diagnosis in veterans diagnosed with traumatic brain injury.

Studies have demonstrated that individuals diagnosed with traumatic brain injury (TBI) frequently use medical and recreational cannabis to treat persistent symptoms of TBI, such as chronic pain and sleep disturbances, which can lead to cannabis use disorder (CUD). We aimed to determine the Veterans Health Administration (VHA) healthcare utilization and costs associated with CUD and dementia diagnosis in veterans with TBI. This observational study used administrative datasets from the population of post-9/11 veterans from the Long-term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium and the VA Data Warehouse. We compared the differential VHA costs among the following cohorts of veterans: (1) No dementia diagnosis and No CUD group, (2) Dementia diagnosis only (Dementia only), (3) CUD only, and (4) comorbid dementia diagnosis and CUD (Dementia and CUD). Generalized estimating equations and negative binomial regression models were used to estimate total annual costs (inflation-adjusted) and the incidence rate of healthcare utilization, respectively, by dementia diagnosis and CUD status. Data from 387,770 veterans with TBI (88.4% men; median [interquartile range (IQR)] age at the time of TBI: 30 [14] years; 63.5% white) were followed from 2000 to 2020. Overall, we observed a trend of gradually increasing healthcare costs 5 years after TBI onset. Interestingly, in this cohort of veterans within 5 years of TBI, we observed substantial healthcare costs in the Dementia only group (peak = $46,808) that were not observed in the CUD and dementia group. Relative to those without either condition, the annual total VHA costs were $3,368 higher in the CUD only group, while no significant differences were observed in the Dementia only and Dementia and CUD groups. The findings suggest that those in the Dementia only group might be getting their healthcare needs met more quickly and within 5 years of TBI diagnosis, whereas veterans in the Dementia and CUD group are not receiving early care, resulting in higher long-term healthcare costs. Further investigations should examine what impact the timing of dementia and CUD diagnoses have on specific categories of inpatient and outpatient care in VA and community care facilities.

Impact of increasing one-carbon metabolites on traumatic brain injury outcome using pre-clinical models.

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

VCE-005.1, an hypoxia mimetic betulinic acid derivative, induces angiogenesis and shows efficacy in a murine model of traumatic brain injury

One of the main global causes of mortality and morbidity is traumatic brain injury (TBI). Neuroinflammation and brain-blood barrier (BBB) disruption play a pivotal role in the pathogenesis of acute and chronic TBI onset. The activation of the hypoxia pathway is a promising approach for CNS neurodegenerative diseases, including TBI. Herein, we have studied the efficacy of VCE-005.1, a betulinic acid hydroxamate, against acute neuroinflammation in vitro and on a TBI mouse model. The effect of VCE-005.1 on the HIF pathway in endothelial vascular cells was assessed by western blot, gene expression, in vitro angiogenesis, confocal analysis and MTT assays. In vivo angiogenesis was evaluated through a Matrigel plug model and a mouse model of TBI induced by a controlled cortical impact (CCI) was used to assess VCE-005.1 efficacy. VCE-005.1 stabilized HIF-1α through a mechanism that involved AMPK and stimulated the expression of HIF-dependent genes. VCE-005.1 protected vascular endothelial cells under prooxidant and pro-inflammatory conditions by enhancing TJ protein expression and induced angiogenesis both in vitro and in vivo. Furthermore, in CCI model, VCE-005.1 greatly improved locomotor coordination, increased neovascularization and preserved BBB integrity that paralleled with a large reduction of peripheral immune cells infiltration, recovering AMPK expression and reducing apoptosis in neuronal cells. Taken together, our results demonstrate that VCE-005.1 is a multitarget compound that shows anti-inflammatory and neuroprotective effects mainly by preventing BBB disruption and has the potential to be further developed pharmacologically in TBI and maybe other neurological conditions that concur with neuroinflammation and BBB disruption.

Acute intranasal treatment with nerve growth factor limits the onset of traumatic brain injury in young rats.

Traumatic brain injury (TBI) comprises a primary injury directly induced by impact, which progresses into a secondary injury leading to neuroinflammation, reactive astrogliosis, and cognitive and motor damage. To date, treatment of TBI consists solely of palliative therapies that do not prevent and/or limit the outcomes of secondary damage and only stabilize the deficits. The neurotrophin, nerve growth factor (NGF), delivered to the brain parenchyma following intranasal application, could be a useful means of limiting or improving the outcomes of the secondary injury, as suggested by pre-clinical and clinical data. We evaluated the effect of acute intranasal treatment of young (20-postnatal day) rats, with NGF in a TBI model (weight drop/close head), aggravated by hypoxic complications. Immediately after the trauma, rats were intranasally treated with human recombinant NGF (50 μg·kg-1 ), and motor behavioural test, morphometric and biochemical assays were carried out 24 h later. Acute intranasal NGF prevented the onset of TBI-induced motor disabilities, and decreased reactive astrogliosis, microglial activation and IL-1β content, which after TBI develops to the same extent in the impact zone and the hypothalamus. Intranasal application of NGF was effective in decreasing the motor dysfunction and neuroinflammation in the brain of young rats in our model of TBI. This work forms an initial pre-clinical evaluation of the potential of early intranasal NGF treatment in preventing and limiting the disabling outcomes of TBI, a clinical condition that remains one of the unsolved problems of paediatric neurology.

Risk of Migraine after Traumatic Brain Injury and Effects of Injury Management Levels and Treatment Modalities: A Nationwide Population-Based Cohort Study in Taiwan.

Traumatic brain injury (TBI) causes several long-term disabilities, particularly headaches. An association between TBI and subsequent migraine has been reported. However, few longitudinal studies have explained the link between migraine and TBI. Moreover, the modifying effects of treatment remain unknown. This retrospective cohort study used records from Taiwan's Longitudinal Health Insurance Database 2005 to evaluate the risk of migraine among patients with TBI and to determine the effects of different treatment modalities. Initially, 187,906 patients, aged ≥ 18 years, who were diagnosed as TBI in 2000, were identified. In total, 151,098 patients with TBI and 604,394 patients without TBI were matched at a 1:4 ratio according to baseline variables during the same observation period. At the end of follow-up, 541 (0.36%) and 1491 (0.23%) patients in the TBI and non-TBI groups, respectively, developed migraine. The TBI group exhibited a higher risk of migraine than the non-TBI group (adjusted HR: 1.484). Major trauma (Injury Severity Score, ISS ≥ 16) was associated with a higher migraine risk than minor trauma (ISS < 16) (adjusted HR: 1.670). However, migraine risk did not differ significantly after surgery or occupational/physical therapy. These findings highlight the importance of long-term follow-up after TBI onset and the need to investigate the underlying pathophysiological link between TBI and subsequent migraine.

Evaluation of Laboratory Variables Related to Diffuse Axonal Injury: A Cross-sectional Study

Background: Diffuse axonal injury (DAI) is an injury that occurs after the onset of traumatic brain injury (TBI), leading to many problems for patients and imposing high costs on the treatment system. Objectives: This study was conducted to investigate the status of laboratory variables in patients with DAI. Methods: This cross-sectional study included 140 patients. Data collection tools were a demographic profile form and magnetic resonance imaging (MRI). Laboratory tests, including glucose, LDL-C, HDL-C, total cholesterol, triglycerides, Hb, HCT, PT, PTT, INR, BUN, creatinine, and CRP were evaluated. Also, specialized devices were used to study the laboratory and radiology variables. Results: Most (61.5%) of the patients were male, 47.1% had a non-governmental occupation, and 55.7% were less than 30 years old. Also, in 87.9% of cases, traffic accidents were the cause of DAI and in 65% of patients, the Glasgow Coma Scale (GCS) was less than 7. In all the laboratory variables differences were observed between the experimental and the control groups. Conclusions: The laboratory variables in patients with DAI had a statistically significant difference compared to the case group, which indicates the negative effect of DAI on laboratory variables. Further studies are required to confirm our results.

Levels of lncRNA GAS5 in Plasma of Patients with Severe Traumatic Brain Injury: Correlation with Systemic Inflammation and Early Outcome.

Scientific efforts continue to concentrate on elucidating the complex molecular mechanisms underlying traumatic brain injury (TBI), and recent reports suggest that epigenetic regulation including long non-coding RNA (lncRNA) is involved. The present study aimed to investigate the plasma concentration of a long non-coding RNA, named growth arrest-specific 5 (GAS5), in a group of 45 patients with severe TBI (sTBI), and to analyze the correlations of GAS5 with TBI onset, injury severity, systemic inflammation, and early outcome of the patients. It was found that plasma GAS5 levels were substantially increased in sTBI patients compared with the relative controls (p < 0.001). Further, significantly higher expression of plasma GAS5 was observed in patients with a Glasgow Coma Scale (GCS) score of less than five (p = 0.002) or unfavorable outcome at discharge (p < 0.001). Circulating GAS5 expression had a negative correlation with GCS score (r = −0.406, p = 0.006), and positive correlations with white blood cell count (r = 0.473, p = 0.001), neutrophil count (r = 0.502, p < 0.001), and neutrophil/lymphocyte ratio (NLR) (r = 0.398, p = 0.007). Univariate and multivariate logistic regression analyses revealed that GCS score (OR = 0.318, 95% CI 0.132–0.767, p = 0.011) and GAS5 (OR = 2.771, 95% CI 1.025–7.494, p = 0.045) were the two independent predictors for early outcome of patients. The receiver operating characteristic (ROC) curves showed good prognostic values of GCS score (AUC = 0.856, 95% CI: 0.719–0.943) and GAS5 expression (AUC = 0.798, 95% CI: 0.651–0.903). Importantly, the combined use of them can improve the prognostic ability of TBI with an AUC of 0.895 (95% CI: 0.767–0.966). Collectively, our study indicated that the levels of lncRNA GAS5 in circulation were elevated following severe TBI and correlated well with injury severity and inflammatory parameters. In addition, GAS5 as well as GCS scores may have the potential to predict the early outcome of TBI patients.

Predictors for 30-Day Readmissions After Traumatic Brain Injury.

To examine predictors for 30-day readmission post-onset of traumatic brain injury (TBI) after initial trauma hospitalization. Retrospective cohort. In total, 5284 patients with an acute TBI admitted from January 1, 2006, through December 31, 2015. Demographic and clinical data after initial TBI onset were extracted from the local trauma registry and matched with the Dallas-Fort Worth Hospital Council registry. Multiple logistic regression analysis was used to determine factors significantly associated with 30-day readmission. Top diagnosis codes for 30-day readmission were also described. Patients were primarily male (64.6%), non-Hispanic White (47.6%), uninsured (35.4%), and aged 46.1 ± 23.3 years. In total, 448 patients (8.5%) had a 30-day readmission. Median cumulative charges for each readmitted subject was $34 313. Factors significantly associated with 30-day readmission were falling as the cause of injury, having increased Charlson Comorbidity Index and Injury Severity Score, and discharging to a skilled nursing facility or long-term acute care. Being uninsured was associated with decreased odds of a 30-day readmission. Top diagnosis codes among the readmission visits included cardiac codes (57.7%), fluid and acid-base disorders (54.8%), and hypertension (50.1%). These data highlight those at risk for 30-day readmission across a diverse population of TBI at a large medical center. Interventions such as health literacy education or patient navigation may help mitigate 30-day readmission for at-risk patients.

The relationship between consciousness and the ascending reticular activating system in patients with traumatic brain injury

BackgroundWe investigated the relationship between consciousness and the ascending reticular activating system (ARAS) by using diffusion tensor tractography (DTT) in patients with traumatic brain injury (TBI).MethodsTwenty-six patients with TBI and 13 healthy control subjects were recruited for this study. Glasgow Coma Scale (GCS) scores were used for evaluation of subject consciousness state at the chronic stage of TBI (at DTT scanning), According to the GCS score, the patient group was divided into two subgroups: A (14 patients;impaired consciousness: GCS score < 15, and B (12 patients;intact consciousness;GCS score = 15). Fractional anisotropy (FA) and tract volume (TV) values were assessed in the lower dorsal and upper ARAS.ResultsThe FA values of the lower dorsal ARAS and the upper ARAS in patient subgroup A were significantly lower than those in patient subgroup B and the control group(p < 0.05). However, the FA and TV values for the lower dorsal ARAS and the upper ARAS were not significantly different between patient subgroup B and the control group(p > 0.05). The FA value of the lower dorsal ARAS(r = 0.473,p < 0.05) and the TV of upper ARAS(r = 0.484,p < 0.05) had moderate positive correlations with the GCS score. The FA value of the upper ARAS had a strong positive correlation with the GCS score of the patient group(r = 0.780,p < 0.05).ConclusionsWe detected a close relationship between consciousness at the chronic stage of TBI and injuries of the lower dorsal and upper ARAS (especially, the upper ARAS) in patients who showed impaired consciousness at the onset of TBI. We believe that our results can be useful during the development of therapeutic strategies for patients with impaired consciousness following TBI.Trial registrationYUMC 2019–06–032-003. Retrospectively registered 06 Jun 2020.

Understanding Traumatic Brain Injury From a Gestalt Approach

This article proposes ways in which the theories, philosophies, and techniques of Gestalt therapy can assist rehabilitation counselors to better understand traumatic brain injury (TBI). The article describes the central tenets of Gestalt therapy and its unique fit to TBI. Discussion focuses on how an appreciation of Gestalt therapy can assist rehabilitation counselors to understand and address the psychological, familial, and service system implications of TBI. A conceptual framework is presented on the pathways of maladjustment and adjustment to living with TBI from a Gestalt perspective. A central assumption of this model is that without intervention, the onset of TBI activates a process of maladjustment for many persons with TBI and their family caregivers expressed by fragmentation, unfinished business, and lack of self-awareness. The model underscores the importance of rehabilitation counselor attention on both individual and contextual levels.

Aggravating effects of treadmill exercises during the early-onset period in a rat traumatic brain injury model: When should rehabilitation exercises be initiated?

Physical exercise is one of the best interventions for improving traumatic brain injury (TBI) outcomes. However, an argument has been raised regarding the timing at which physical exercise should be initiated. In this study, male Wistar rats were subjected to stab wounding of the right hemisphere to develop a TBI model and were forced to walk once on a treadmill at a 5-m/min pace at 24h or 48h after TBI for 10min. Injured brain tissue was dissected after TBI to evaluate the effects of exercise. Behavioral abnormalities and motor impairment were assessed by various behavioral tests between 2 and 3 weeks after TBI. Exercise did not affect the circulating corticosterone levels and the weight of the adrenal glands. Exercise particularly that at 24h, worsened the motor impairment of the left forelimbs. Quantitative reverse-transcription polymerase chain reaction showed that exercise at 24h increased proinflammatory cytokines and chemokines on the third day while suppressing the proinflammatory reactions on the fourth day. Exercise at both time points decreased expression of transforming growth factor (TGF) β1 and its receptor TGFβR1. Exercise at 24h increased phosphorylation of IκB kinase on the fourth day, which may be correlated with the decreased effects of TGFβ1. Even a low-intensity exercise activity could cause deleterious effects when it is initiated within 48h after the onset of severe TBI, probably because of the resulting proinflammatory effects. Therefore, rehabilitation exercise programs should be initiated after 48h of TBI onset.

Decreased Risk of Dementia Among Patients With Traumatic Brain Injury Receiving Acupuncture Treatment: A Population-Based Retrospective Cohort Study.

We conducted a longitudinal cohort study comparing the effect of acupuncture on the risk of dementia in Taiwanese individuals with traumatic brain injury (TBI). A national health insurance database was used to identify 15 440 newly diagnosed TBI patients 20 to 70 years old between 1998 and 2007. Of the identified patients, 6308 received acupuncture following the onset of TBI (acupuncture users) and 9132 patients did not receive acupuncture (nonacupuncture users). All enrollees were followed until the end of 2012 to record incident cases of dementia. A Cox proportional hazards regression model was used to compute adjusted hazard ratios for the relationship of acupuncture use with dementia. During the follow-up period, 249 acupuncture users and 810 nonacupuncture users developed dementia, corresponding to incidence rates of 6.11 and 9.64 per 1000 person-years, respectively. Use of acupuncture was significantly associated with a lower risk of dementia. Those who received more than 5 sessions of acupuncture benefited most from it. Adding acupuncture to the clinical management of patients with TBI may benefit these patients by decreasing their risk of developing dementia.

The Importance of Therapeutic Time Window in the Treatment of Traumatic Brain Injury.

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

Effects of Minocycline on Neurological Outcomes In Patients With Acute Traumatic Brain Injury: A Pilot Study.

Traumatic brain injury (TBI) is a public health problem worldwide. Secondary damage of brain injury begins within a few minutes after the trauma and can last a long time. It can be reversible, unlike primary injury. Therefore, therapeutic intervention can be used. The aims of this study were to assess the effects of minocycline on neurological function and serum S100B protein and neuron-specific enolase (NSE) levels in patients with moderate to severe TBI. Patients with acute onset of TBI and surgical evacuation of hematoma were randomized to receive either minocycline 100 mg orally twice daily or placebo for 7 days. The primary outcomes included changes in level of S100B and NSE at different time points during the trial. Additionally, changes in Glasgow coma scale (GCS) score were evaluated. The Glasgow Outcome Scale-Extended (GOS-E) score at 6 months after injury was assessed in discharge patients. Thirty four patients were randomized into the placebo (n = 20) and treatment (n = 14) groups. There was a marginal statistically significant differences in the normalized value of S100B between groups (p < 0.1). The reduction in serum NSE level from baseline to day 5 was statistically significant (p = 0.01) in minocycline group while it was not significantly decrease in placebo group (p = 0.2). Also, GCS improvement over time within the minocycline group was significant (p = 0.04) while was not significant in placebo group (p = 0.11). The GOS-E scores were not significantly different between minocycline and placebo group. Based on this study, it seems that the use of minocycline may be effective in acute TBI.

Prefrontal and temporal cortical thickness in adolescents with traumatic brain injury

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

The Role of Magnetic Resonance Imaging in the Prediction of Minimally Conscious State After Traumatic Brain Injury

To establish a simple and feasible model of magnetic resonance imaging (MRI) for prediction of minimally conscious state in unconscious patients (≥2 weeks) after severe traumatic brain injury (TBI). MRI examinations were performed in 73 patients 4.5 weeks ± 1.6 (range, 2-8 weeks) after TBI. Brain lesions on MRI, age, sex, cause of injury, Glasgow Coma Scale (GCS) score, and decompressive craniectomy were retrospectively analyzed. Outcome was assessed at 12 months from the onset of TBI. Of 73 patients, 39 were minimally conscious and 34 were unconscious at the endpoint. Binary logistic regression demonstrated that cause of injury (P= 0.036), GCS score (P= 0.011), and lesions of the thalamus (P=0.002) and brainstem (P= 0.012) shown on MRI were closely associated with the outcome of minimally conscious state. The overall correct prediction of the logistic model was 90.4%. The combination of MRI findings and other clinical data offers neurosurgeons substantial information about primary and secondary injuries of the patients with TBI, which allows a more accurate prediction of prognosis than a single GCS score or MRI findings alone. The regression model established in this study is simple and effective in predicting long-term unconscious state and minimally conscious state in patients after severe TBI.

Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4/NF-κB signaling pathway in experimental traumatic brain injury.

Previous research has demonstrated that traumatic brain injury (TBI) activates autophagy and a neuroinflammatory cascade that contributes to substantial neuronal damage and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of this cascade. In the present study, we investigated the hypothesis that resveratrol (RV), a natural polyphenolic compound with potent multifaceted properties, alleviates brain damage mediated by TLR4 following TBI. Adult male Sprague Dawley rats, subjected to controlled cortical impact (CCI) injury, were intraperitoneally injected with RV (100 mg/kg, daily for 3 days) after the onset of TBI. The results demonstrated that RV significantly reduced brain edema, motor deficit, neuronal loss and improved spatial cognitive function. Double immunolabeling demonstrated that RV decreased microtubule-associated protein 1 light chain 3 (LC3), TLR4-positive cells co-labeled with the hippocampal neurons, and RV also significantly reduced the number of TLR4-positive neuron-specific nuclear protein (NeuN) cells following TBI. Western blot analysis revealed that RV significantly reduced the protein expression of the autophagy marker proteins, LC3II and Beclin1, in the hippocampus compared with that in the TBI group. Furthermore, the levels of TLR4 and its known downstream signaling molecules, nuclear factor-κB (NF-κB), and the inflammatory cytokines, interleukin (IL)-1β and tumor necrosis factor (TNF)-α were also decreased after RV treatment. Our results suggest that RV reduces neuronal autophagy and inflammatory reactions in a rat model of TBI. Thus, we suggest that the neuroprotective effect of RV is associated with the TLR4/NF-κB signaling pathway.

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

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

An experimental study: does the neuroprotective effect increase when hypothermia deepens after traumatic brain injury?

Background:Experimental approaches have been promising with the use of therapeutic hypothermia after Traumatic Brain Injury (TBI) whereas clinical data have not supported its efficacy.Objectives:This study aimed to investigate whether using selective deeper brain cooling correlates with a more neuroprotective effect on Intracranial Pressure (ICP) increments following TBI in rats.Materials and Methods:Adult male Sprague-Dawley rats (mean weight = 300 g; n = 25) were subjected to brain injury using a modified Marmarou method. Immediately after the onset of TBI, rats were randomized into three groups. Selective brain cooling was applied around the head using ice packages. Intracranial Temperature (ICT) and ICP were continuously measured at 0, 30, 60, 120, and 180 minutes and recorded for all groups. Group 1 (n = 5) was normothermia and was assigned as the control group. Group 2 (n = 10) received moderate hypothermia with a target ICT of between 32°C - 33°C and Group 3 (n = 10) was given a deeper hypothermia with a target ICT of below 32°C.Results:All subjects reached the target ICT by the 30th minute of hypothermia induction. The ICT was significantly different in Group 2 compared to Group 1 only at the 120th minute (P = 0.017), while ICP was significantly lower starting from the 30th minute (P = 0.015). The ICT was significantly lower in Group 3 compared to Groups 1 and 2 starting from the 30th minute (P = 0.001 and P = 0.003, respectively). The ICP was significantly lower in Group 3 compared to Group 1 starting from 30th minute (P = 0.001); however, a significant difference in ICP between Group 3 and Group 2 was observed only at the 180th minute (P = 0.047).Conclusions:Results of this study indicate that selective brain cooling is an effective method of decreasing ICP in rats; however, the deeper hypothermia caused a greater decrease in ICP three hours after hypothermia induction.

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

BackgroundThe neuroprotective mechanisms of hyperbaric oxygen (HBO) therapy on traumatic brain injury (TBI) remain unclear, especially neuronal apoptosis associations such as the expression of tumor necrosis factor alpha (TNF-α), transforming growth-interacting factor (TGIF), and TGF-β1 after TBI. The aim of this study was to investigate the neuroprotective effects of HBO therapy in a rat model of TBI. Materials and methodsThe experimental rats were randomly divided into three groups as follows: TBI + normobaric air (21% O2 at one absolute atmosphere), TBI + HBO, and sham-operated normobaric air. The TBI + HBO rats received 100% O2 at 2.0 absolute atmosphere for 1 h immediately after TBI. Local and systemic TNF-α expression, neuropathology, levels of the neuronal apoptosis-associated proteins TGIF and TGF-β1, and functional outcome were evaluated 72 h after the onset of TBI. ResultsCompared to the TBI control groups, the running speed of rats on the TreadScan after TBI was significantly attenuated by HBO therapy. The TBI-induced local and systemic TNF-α expression, neuronal damage score, and neuronal apoptosis were also significantly reduced by HBO therapy. Moreover, HBO treatment attenuated the expression of TGIF but increased TGF-β1 expression in neurons. ConclusionsWe concluded that treatment of TBI with HBO during the acute phase of injury can decrease local and systemic proinflammatory cytokine TNF-α production, resulting in neuroprotective effects. We also suggest that decreased levels of TGIF and increased levels of TGF-β in the injured cortex leading to decreased neuronal apoptosis is one mechanism by which functional recovery may occur.