Treatment Of Traumatic Brain Injury Research Articles

Human umbilical cord-derived mesenchymal stem cells-harvested mitochondrial transplantation improved motor function in TBI models through rescuing neuronal cells from apoptosis and alleviating astrogliosis and microglia activation

Each year, traumatic brain injury (TBI) causes a high rate of mortality throughout the world and those who survive have lasting disabilities. Given that the brain is a particularly dynamic organ with a high energy consumption rate, the inefficiency of current TBI treatment options highlights the necessity of repairing damaged brain tissue at the cellular and molecular levels, which according to research is aggravated due to ATP deficiency and reactive oxygen species surplus. Taking into account that mitochondria contribute to generating energy and controlling cellular stress, mitochondrial transplantation as a new treatment approach has lately reduced complications in a number of diseases by supplying healthy and functional mitochondria to the damaged tissue. For this reason, in this study, we used this technique to transplant human umbilical cord-derived mesenchymal stem cells (hUC-MSCs)-derived mitochondria as a suitable source for mitochondrial isolation into rat models of TBI to examine its therapeutic benefit and the results showed that the successful mitochondrial internalisation in the neuronal cells significantly reduced the number of brain cells undergoing apoptosis, alleviated astrogliosis and microglia activation, retained normal brain morphology and cytoarchitecture, and improved sensorimotor functions in a rat model of TBI. These data indicate that human umbilical cord-derived mesenchymal stem cells-isolated mitochondrial transplantation improves motor function in a rat model of TBI via rescuing neuronal cells from apoptosis and alleviating astrogliosis and microglia activation, maybe as a result of restoring the lost mitochondrial content.

Modulation of neurotrophic factors in the treatment of dementia, stroke and TBI: Effects of Cerebrolysin.

Neurotrophic factors (NTFs) are involved in the pathophysiology of neurological disorders such as dementia, stroke and traumatic brain injury (TBI), and constitute molecular targets of high interest for the therapy of these pathologies. In this review we provide an overview of current knowledge of the definition, discovery and mode of action of five NTFs, nerve growth factor, insulin-like growth factor 1, brain derived NTF, vascular endothelial growth factorand tumor necrosis factor alpha; as well as on their contribution to brain pathology and potential therapeutic use in dementia, stroke and TBI. Within the concept of NTFs in the treatment of these pathologies, we also review the neuropeptide preparation Cerebrolysin, which has been shown to resemble the activities of NTFs and to modulate the expression level of endogenous NTFs. Cerebrolysin has demonstrated beneficial treatment capabilities in vitro and in clinical studies, which are discussed within the context of the biochemistry of NTFs. The review focuses on the interactions of different NTFs, rather than addressing a single NTF, by outlining their signaling network and by reviewing their effect on clinical outcome in prevalent brain pathologies. The effects of the interactions of these NTFs and Cerebrolysin on neuroplasticity, neurogenesis, angiogenesis and inflammation, and their relevance for the treatment of dementia, stroke and TBI are summarized.

MiR-211-5p targeting MMP9 regulates the expressions of AQP4 in traumatic brain injury.

The abnormal expression of matrix metalloproteinase 9 (MMP9) and Aquaporin 4 (AQP4) closely associates with the traumatic brain injury (TBI) development. Here, we investigated the relationship between miR-211-5p and MMP9/AQP4 axis in TBI patients and astrocyte cells. Demographics, clinical features, and cerebrospinal fluid (CSF) samples were collected from traumatic brain injury (TBI) patients (n = 96) and controls (n = 30) for pathological and gene expression analyses. Luciferase activity assay and gene expression analyses were performed to dissect the regulatory mechanism of miR-211-5p on MMP9/AQP4 in human astrocyte cells. miR-211-5p mRNA was significantly decreased in the CSF of TBI patients, which positively correlated with the expression of both MMP9 and AQP4. miR-211-5p could target MMP9 directly in SVG P12 cells. Overexpression of miR-211-5p decreased the expression of MMP9, on the contrary, knockdown miR-211-5p through inhibitors increased the expression of both MMP9 and AQP4. miR-211-5p inhibits the MMP9/AQP4 axis in human astrocyte cells, which represents a promising approach for the TBI treatment.

Clinical Diagnosis and Management of Traumatic Acute Intracranial Subdural Hematoma: Review Article

Traumatic brain injury (TBI) is the leading cause of death and disabling conditions in persons. The frequency and severity of head injuries have both decreased as a result of numerous industrial safety improvements, the installation of airbags in automobiles, and the enforcement of speed restrictions. TBI survivorship has increased due to advancements in emergency response times and acute care, but this has also increased the need for accurate ways to detect individuals at risk of subsequent diseases. Pupil reactivity, the Glasgow Coma Scale, and head computed tomography are currently the main clinical signs indicating the existence of brain damage. The current review will cover the clinical presentation, diagnosis, and treatment of TBI,

Loading neural stem cells on hydrogel scaffold improves cell retention rate and promotes functional recovery in traumatic brain injury.

Neural stem cell (NSC) has gained considerable attention in traumatic brain injury (TBI) treatment because of their ability to replenish dysfunctional neurons and stimulate endogenous neurorestorative processes. However, their therapeutic effects are hindered by the low cell retention rate after transplantation into the dynamic brain. In this study, we found cerebrospinal fluid (CSF) flow after TBI is an important factor associated with cell loss following NSC transplantation. Recently, several studies have shown that hydrogels could serve as a beneficial carrier for stem cell transplantation, which provides a solution to prevent CSF flow-induced cell loss after TBI. For this purpose, we evaluated three different hydrogel scaffolds and found the gelatin methacrylate (GelMA)/sodium alginate (Alg) (GelMA/Alg) hydrogel scaffold showed the best capabilities for NSC adherence, growth, and differentiation. Additionally, we detected that pre-differentiated NSCs, which were loaded on the GelMA/Alg hydrogel and cultured for 7 days in neuronal differentiation medium (NSC [7d]), had the highest cell retention rate after CSF impact. Next, the neuroprotective effects of the NSC-loaded GelMA/Alg hydrogel scaffold were evaluated in a rat model of TBI. NSC [7d]-loaded GelMA/Alg markedly decreased microglial activation and neuronal death in the acute phase, reduced tissue loss, alleviated astrogliosis, promoted neurogenesis, and improved neurological recovery in the chronic phase. In summary, we demonstrated that the integration with the GelMA/Alg and modification of NSC differentiation could inhibit the influence of CSF flow on transplanted NSCs, leading to increased number of retained NSCs and improved neuroprotective effects, providing a promising alternative for TBI treatment.

Traumatic Brain Injury in a Well: A Modular Three-Dimensional Printed Tool for Inducing Traumatic Brain Injury In vitro.

Traumatic brain injury (TBI) is a major health problem that affects millions of persons worldwide every year among all age groups, mainly young children, and elderly persons. It is the leading cause of death for children under the age of 16 and is highly correlated with a variety of neuronal disorders, such as epilepsy, and neurodegenerative disease, such as Alzheimer's disease or amyotrophic lateral sclerosis. Over the past few decades, our comprehension of the molecular pathway of TBI has improved, yet despite being a major public health issue, there is currently no U.S. Food and Drug Administration-approved treatment for TBI, and a gap remains between these advances and their application to the clinical treatment of TBI. One of the major hurdles for pushing TBI research forward is the accessibility of TBI models and tools. Most of the TBI models require costume-made, complex, and expensive equipment, which often requires special knowledge to operate. In this study, we present a modular, three-dimensional printed TBI induction device, which induces, by the pulse of a pressure shock, a TBI-like injury on any standard cell-culture tool. Moreover, we demonstrate that our device can be used on multiple systems and cell types and can induce repetitive TBIs, which is very common in clinical TBI. Further, we demonstrate that our platform can recapitulate the hallmarks of TBI, which include cell death, decrease in neuronal functionality, axonal swelling (for neurons), and increase permeability (for endothelium). In addition, in view of the continued discussion on the need, benefits, and ethics of the use of animals in scientific research, this in vitro, high-throughput platform will make TBI research more accessible to other labs that prefer to avoid the use of animals yet are interested in this field. We believe that this will enable us to push the field forward and facilitate/accelerate the availability of novel treatments.

Factors Associated with Adverse Outcomes in Cameroonian Patients with Traumatic Brain Injury: A Cross-Sectional Study.

The burden of traumatic brain injury (TBI) disproportionately affects low- and middle-income countries. In Cameroon, the estimated annual incidence rate is 572 cases per 100,000 people. This study investigated factors associated with adverse outcomes in the management of Cameroonian patients with TBI. This cross-sectional study included all patients with TBI treated between January 1 and December 31, 2018, at 2 Cameroonian referral hospitals. Sociodemographic and clinical data were extracted from patient charts and admission registries and analyzed with SPSS v.26. Independent t tests, odds ratios, and cumulative mortality hazard rates were computed. A P-value <0.05 was considered statistically significant. Also, binomial regression analyses were calculated. One hundred seventy-one patients aged 38.63±20.46years old received treatment for TBI. Most patients were male (78.9%), Cameroonian (98.2%), from urban areas (75.4%), and uninsured (88.8%). The average admission length was 11.23±10.71days, during which 27.5% of patients received surgical treatment while 72.5% received non-surgical (conservative) management. From postdischarge day 12 onwards, surgically-treated patients had a greater cumulative mortality hazard rate than conservatively-treated patients. By 28days postdischarge, 66.1% of patients had recovered completely [Glasgow Outcome Scale (GOS)= 5], 23.4% had a disability (GOS=2-4), and 10.5% expired (GOS=1). Complete recovery was associated with the absence of severe TBI (B=-1.42, standard error [SE]=0.52, P= 0.006), disability was associated with increased injury-to-admission delay (B=-1.27, SE=0.48, P= 0.009), and death was associated with severe TBI (B= 3.16, SE=0.73, P < 0.001). We identified factors associated with unfavorable outcomes among Cameroonian patients with TBI. These results can inform triage and referral practices and aid policymakers in developing context-specific prehospital guidelines.

Edaravone in the treatment of concussion and post-concussion syndrome

ABSTRACT. The review describes the pathogenetic mechanisms of the development of traumatic brain injury (TBI), contusion and post-concussion syndrome, and presents the modern possibilities of their pharmacotherapy. The analysis of experimental and clinical studies showed that the multifactorial effect of edaravone on the main pathogenetic links of brain damage in TBI and numerous positive clinical effects make edaravone a promising drug in the treatment of TBI, concussion and post-concussive syndrome.

Identifying Unique Symptom Groups Following Mild Traumatic Brain Injury Using the Neurobehavioral Symptom Inventory and PTSD Checklist-5 in Military Personnel: A Bifactor Analysis.

To identify both shared and unique groups of posttraumatic stress and postconcussive symptoms using bifactor analysis. Two large military outpatient traumatic brain injury (TBI) rehabilitation clinics in the Southwestern United States. A sample of 1476 Active Duty Service Members seeking treatment for a mild TBI sustained more than 30 days previously, without history of moderate or severe TBI, who completed measures of postconcussive and posttraumatic stress symptoms assessed at clinic intake. Observational, correlational study with data taken from an institutional review board-approved clinical registry study. Neurobehavioral Symptom Inventory (NSI) and Posttraumatic Stress Disorder (PTSD) Checklist for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) ( DSM-V ) (PCL-5). Concurrent measures were Patient Health Questionnaire (PHQ-8), Pittsburgh Sleep Quality Index (PSQI), and Headache Impact Test (HIT-6). Results identified a bifactor model demonstrating unique posttraumatic stress, depressive, cognitive, and neurological/somatic symptom groups that were still evident after accounting for a universal factor representing general distress. These symptom groups were differentially related to concurrently measured clinical outcomes. Use of a bifactor structure may help derive clinically useful signals from self-reported symptoms among Active Duty Service Members seeking outpatient treatment for mild TBI.

Guillain-Barré Syndrome with Incomplete Oculomotor Nerve Palsy after Traumatic Brain Injury: Case Report and Literature Review

Guillain-Barré syndrome (GBS) is a severe peripheral neuroinflammatory demyelinating disease characterized by symmetrical progressive limb weakness, which can be accompanied by cranial nerve and sensory disturbances. There is usually a history of bacterial or viral infection prior to onset. GBS is rarely seen after traumatic brain injury (TBI). We report a case of a 66-year-old male patient who presented with dilated pupils, followed by respiratory failure and symmetrical quadriplegia during a conservative treatment for TBI. He was eventually diagnosed with GBS and was treated with intravenous immunoglobulin, followed by rehabilitation therapy with a good recovery. We summarize previous similar cases and analyze possible causes. It is suggested that the possibility of GBS should be considered when unexplained symptoms occurred in patients with TBI, such as respiratory failure, dilated pupils, and limb weakness.

Satureja khuzistanica Jamzad essential oil and pure carvacrol attenuate TBI-induced inflammation and apoptosis via NF-κB and caspase-3 regulation in the male rat brain

Traumatic brain injury (TBI) causes progressive dysfunction that induces biochemical and metabolic changes that lead to cell death. Nevertheless, there is no definitive FDA-approved therapy for TBI treatment. Our previous immunohistochemical results indicated that the cost-effective natural Iranian medicine, Satureja khuzistanica Jamzad essential oil (SKEO), which consists of 94.16% carvacrol (CAR), has beneficial effects such as reducing neuronal death and inflammatory markers, as well as activating astrocytes and improving neurological outcomes. However, the molecular mechanisms of these neuroprotective effects have not yet been elucidated. This study investigated the possible mechanisms involved in the anti-inflammatory and anti-apoptotic properties of SKEO and CAR after TBI induction. Eighty-four male Wistar rats were randomly divided into six groups: Sham, TBI, TBI + Vehicle, TBI + CAR (100 and 200 mg/kg), and TBI + SKEO (200 mg/kg) groups. After establishing the “Marmarou” weight drop model, diffuse TBI was induced in the rat brain. Thirty minutes after TBI induction, SKEO & CAR were intraperitoneally injected. One day after TBI, injured rats exhibited significant brain edema, neurobehavioral dysfunctions, and neuronal apoptosis. Western blot results revealed upregulation of the levels of cleaved caspase-3, NFκB p65, and Bax/Bcl-2 ratio, which was attenuated by CAR and SKEO (200 mg/kg). Furthermore, the ELISA results showed that CAR treatment markedly prevents the overproduction of the brain pro-inflammatory cytokines, including IL-1β, TNF-α, and IL-6. Moreover, the neuron-specific enolase (NSE) immunohistochemistry results revealed the protective effect of CAR and SKEO on post-TBI neuronal death. The current study revealed that the possible neuroprotective mechanisms of SKEO and CAR might be related to (at least in part) modulating NF-κB regulated inflammation and caspase-3 protein expression. It also suggested that CAR exerts more potent protective effects than SKEO against TBI. Nevertheless, the administration of SKEO and CAR may express a novel therapeutic approach to ameliorate TBI-related secondary phase neuropathological outcomes.

Neuroprotection of NRF2 against Ferroptosis after Traumatic Brain Injury in Mice

Ferroptosis and iron-related redox imbalance aggravate traumatic brain injury (TBI) outcomes. NRF2 is the predominant transcription factor regulating oxidative stress and neuroinflammation in TBI, but its role in iron-induced post-TBI damage is unclear. We investigated ferroptotic neuronal damage in the injured cortex and observed neurological deficits post-TBI. These were ameliorated by the iron chelator deferoxamine (DFO) in wild-type mice. In Nrf2-knockout (Nrf2-/-) mice, more sever ferroptosis and neurological deficits were detected. Dimethyl fumarate (DMF)-mediated NRF2 activation alleviated neural dysfunction in TBI mice, partly due to TBI-induced ferroptosis mitigation. Additionally, FTH-FTL and FSP1 protein levels, associated with iron metabolism and the ferroptotic redox balance, were highly NRF2-dependent post-TBI. Thus, NRF2 is neuroprotective against TBI-induced ferroptosis through both the xCT-GPX4- and FTH-FTL-determined free iron level and the FSP1-regulated redox status. This yields insights into the neuroprotective role of NRF2 in TBI-induced neuronal damage and its potential use in TBI treatment.

Engineered Mesenchymal Stem Cells Over-Expressing BDNF Protect the Brain from Traumatic Brain Injury-Induced Neuronal Death, Neurological Deficits, and Cognitive Impairments.

Traumatic brain injury (TBI) causes transitory or permanent neurological and cognitive impairments, which can intensify over time due to secondary neuronal death. However, no therapy currently exists that can effectively treat brain injury following TBI. Here, we evaluate the therapeutic potential of irradiated engineered human mesenchymal stem cells over-expressing brain-derived neurotrophic factor (BDNF), which we denote by BDNF-eMSCs, in protecting the brain against neuronal death, neurological deficits, and cognitive impairment in TBI rats. BDNF-eMSCs were administered directly into the left lateral ventricle of the brain in rats that received TBI damage. A single administration of BDNF-eMSCs reduced TBI-induced neuronal death and glial activation in the hippocampus, while repeated administration of BDNF-eMSCs reduced not only glial activation and delayed neuronal loss but also enhanced hippocampal neurogenesis in TBI rats. In addition, BDNF-eMSCs reduced the lesion area in the damaged brain of the rats. Behaviorally, BDNF-eMSC treatment improved the neurological and cognitive functions of the TBI rats. The results presented in this study demonstrate that BDNF-eMSCs can attenuate TBI-induced brain damage through the suppression of neuronal death and increased neurogenesis, thus enhancing functional recovery after TBI, indicating the significant therapeutic potential of BDNF-eMSCs in the treatment of TBI.

Effects of C1-INH Treatment on Neurobehavioral Sequelae and Late Seizures After Traumatic Brain Injury in a Mouse Model of Controlled Cortical Impact.

C1 human-derived C1 esterase inhibitor (C1-INH) is a U.S. Food and Drig Administration-approved drug with anti-inflammatory actions. In the present study, we investigated the therapeutic effects of C1-INH on acute and chronic neurobehavioral outcomes and on seizures in the chronic stage in a mouse traumatic brain injury (TBI) model. Adult male CD1 mice were subjected to controlled cortical impact and randomly allocated to receive C1-INH or vehicle solution 1 h post-TBI. Effects of C1-INH treatment on inflammatory responses and brain damage after TBI were examined using the Cytometric Bead Array, C5a enzyme-linked immunosorbent assay, Fluoro-Jade C staining, and Nissl staining. Neurobehavioral outcomes after TBI were assessed with modified neurological severity scores, the rotarod and open field tests, and the active place avoidance task. Video-electroencephalographic monitoring was performed in the 15th and 16th weeks after TBI to document epileptic seizures. We found that C1-INH treatment reduced TNFα expression and alleviated brain damage. Treatment with C1-INH improved neurological functions, increased locomotor activity, alleviated anxiety-like behavior, and exhibited an effect on seizures in the chronic stage after TBI. These findings suggest that C1-INH has beneficial effects on the treatment of TBI.

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.

Predictive model for early functional outcomes following acute care after traumatic brain injuries: A machine learning-based development and validation study

Few studies on early functional outcomes following acute care after traumatic brain injury (TBI) are available. The aim of this study was to develop and validate a predictive model for functional outcomes at discharge for TBI patients using machine learning methods. In this retrospective study, data from 5281 TBI patients admitted for acute care who were identified in the Beijing hospital discharge abstract database were analysed. Data from 4181 patients in 52 tertiary hospitals were used for model derivation and internal validation. Data from 1100 patients in 21 secondary hospitals were used for external validation. A poor outcome was defined as a Barthel Index (BI) score ≤ 60 at discharge. Logistic regression, XGBoost, random forest, decision tree, and back propagation neural network models were used to fit classification models. Performance was evaluated by the area under the receiver operating characteristic curve (AUC), the area under the precision-recall curve (AP), calibration plots, sensitivity/recall, specificity, positive predictive value (PPV)/precision, negative predictive value (NPV) and F1-score. Compared to the other models, the random forest model demonstrated superior performance in internal validation (AUC of 0.856, AP of 0.786, and F1-score of 0.724) and external validation (AUC of 0.779, AP of 0.630, and F1-score of 0.604). The sensitivity/recall, specificity, PPV/precision, and NPV of the model were 71.8%, 69.2%, 52.2%, and 84.0%, respectively, in external validation. The BI score at admission, age, use of nonsurgical treatment, neurosurgery status, and modified Charlson Comorbidity Index were identified as the top 5 predictors for functional outcome at discharge. We established a random forest model that performed well in predicting early functional outcomes following acute care after TBI. The model has utility for informing decision-making regarding patient management and discharge planning and for facilitating health care quality assessment and resource allocation for TBI treatment.

Differences in Risk of Alzheimer's Disease Following Later-Life Traumatic Brain Injury in Veteran and Civilian Populations.

To directly compare the effect of incident age 68+ traumatic brain injury (TBI) on the risk of diagnosis of clinical Alzheimer's disease (AD) in the general population of older adults, and between male veterans and nonveterans; to assess how this effect changes with time since TBI. Community-dwelling traditional Medicare beneficiaries 68 years or older from the Health and Retirement Study (HRS). Fine-Gray models combined with inverse-probability weighting were used to identify associations between incident TBI, post-TBI duration, and TBI treatment intensity, with a diagnosis of clinical AD dementia. The study included 16 829 older adults followed over the 1991-2015 period. For analyses of veteran-specific risks, 4281 veteran males and 3093 nonveteran males were identified. Analysis of veteran females was unfeasible due to the age structure of the population. Information on occurrence(s) of TBI, and onset of AD and risk-related comorbidities was constructed from individual-level HRS-linked Medicare claim records while demographic and socioeconomic risk factors were based on the survey data. Later-life TBI was strongly associated with increased clinical AD risk in the full sample (pseudo-hazard ratio [HR]: 3.22; 95% confidence interval [CI]: 2.57-4.05) and in veteran/nonveteran males (HR: 5.31; CI: 3.42-7.94), especially those requiring high-intensity/duration care (HR: 1.58; CI: 1.29-1.91). Effect magnitude decreased with time following TBI (HR: 0.72: CI: 0.68-0.80). Later-life TBI was strongly associated with increased AD risk, especially in those requiring high-intensity/duration care. Effect magnitude decreased with time following TBI. Univariate analysis showed no differences in AD risk between veterans and nonveterans, while the protective effect associated with veteran status in Fine-Gray models was largely due to differences in demographics, socioeconomics, and morbidity. Future longitudinal studies incorporating diagnostic procedures and documentation quantifying lifetime TBI events are necessary to uncover pathophysiological mediating and/or moderating mechanisms between TBI and AD.

Role of hyperbaric oxygen therapy in PDGF-BB-mediated astrogliosis in traumatic brain injury rats associated with ERK1/2 signaling pathway inhibition

BackgroundHyperbaric oxygen (HBO) plays positive roles in the therapy of traumatic brain injury (TBI); however, the mechanism underlying its effects on TBI is largely unknown. The study aims to elucidate the molecular mechanism implicated with the interaction between platelet-derived growth factor-BB (PDGF-BB) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway, which may play critical roles during HBO treatment both in the astrocyte scratching model in vitro and rat TBI model in vivo.MethodsChanges in neurological function and wound healing were evaluated using the neurological severity scores (NSS) scale, immunohistochemistry, western blotting, and qRT-PCR, respectively.ResultsThe results showed that PDGF-BBi (PDGB interfered with small RNA) dramatically improves neuronal viability in vitro when transfected into the scratched astrocytes derived from the cerebral cortex of neonatal rats. Moreover, in vivo experiments revealed that HBO therapy substantially elevated the NSS scores and simultaneously reduced the mortality in TBI rats, as indicated by the NSS scales. Notably, HBO therapy was found to possess the ability to inhibit glial cell proliferation, promote the regeneration of neurons and synapses, and ultimately facilitate the wound healing, as revealed by immunohistochemistry and glial scar formation found in TBI rats. Importantly, HBO markedly decreased the expression levels of PDGF-BB and ERK1/2. It can clearly be seen that downregulated PDGF-BB and ERK1/2 levels were corresponding with the status of significant amelioration of the therapeutic effect of HBO. Conversely, the upregulation of PDGF-BB and ERK1/2 levels was in line with the opposite effect.ConclusionIt has been concluded that HBO therapy may play its active role in TBI treatment dependent on astrogliosis inhibition, which may be achieved by downregulating the ERK1/2 signaling pathway mediated by PDGF-BB.

Recent Advances in Biomaterials-Based Therapies for Alleviation and Regeneration of Traumatic Brain Injury.

Traumatic brain injury (TBI), a major public health problem accompanied with numerous complications, usually leads to serve disability and huge financial burden. The adverse and unfavorable pathological environment triggers a series of secondary injuries, resulting in serious loss of nerve function and huge obstacle of endogenous nerve regeneration. With the advances in adaptive tissue regeneration biomaterials, regulation of detrimental microenvironment to reduce the secondary injury and to promote the neurogenesis becomes possible. The adaptive biomaterials could respond and regulate biochemical, cellular, and physiological events in the secondary injury, including excitotoxicity, oxidative stress, and neuroinflammation, to rebuild circumstances suitable for regeneration. In this review, the development of pathology after TBI is discussed, followed by the introduction of adaptive biomaterials based on various pathological characteristics. The adaptive biomaterials carried with neurotrophic factors and stem cells for TBI treatment are then summarized. Finally, the current drawbacks and future perspective of biomaterials for TBI treatment are suggested.

Challenges in the Treatment of Severe Traumatic Brain Injury Based on Data in the Japan Neurotrauma Data Bank.

The Japan Neurotrauma Data Bank is a source of epidemiological data for patients with severe traumatic brain injury (TBI) and is sponsored by the Japan Society of Neurotraumatology. In this report, we examined the changes in the treatment of severe TBI in Japan based on data of the Japan Neurotrauma Data Bank. Controlling and decreasing intracranial pressure (ICP) are the primary objective of severe TBI treatment. Brain-oriented whole-body control or neurocritical care, including control of cerebral perfusion pressure, respiration, and infusion, are also increasingly considered important because cerebral tissues require oxygenation to improve the outcomes of patients with severe TBI. The introduction of neurocritical care in Japan was delayed compared with that in Western countries. However, the rate of ICP monitoring increased from 28.0% in 2009 to 36.7% in 2015 and is currently likely to be higher. Neurocritical care has also become more common, but the functional prognosis of patients has not significantly improved in Japan. Changes in the background of patients with severe TBI suggest the need for improvement of acute-phase treatment for elderly patients. Appropriate social rehabilitation from the subacute to chronic phases and introduction of cellular therapeutics are also needed for patients with TBI.