Treatment Of Traumatic Brain Injury Research Articles

Futuristic Trends in Occupational Therapy Interventions for Traumatic Brain Injury

Futuristic Trends in Occupational Therapy Interventions for Traumatic Brain Injury

Decompressive craniectomy as a second/third-tier intervention in traumatic brain injury: A multicenter observational study

ObjectivesRESCUEicp studied decompressive craniectomy (DC) applied as third-tier option in severe traumatic brain injury (TBI) patients in a randomized controlled setting and demonstrated a decrease in mortality with similar rates of favorable outcome in the DC group compared to the medical management group. In many centers, DC is being used in combination with other second/third-tier therapies. The aim of the present study is to investigate outcomes from DC in a prospective non-RCT context. MethodsThis is a prospective observational study of 2 patient cohorts: one from the University Hospitals Leuven (2008–2016) and one from the Brain-IT study, a European multicenter database (2003–2005). In thirty-seven patients with refractory elevated intracranial pressure who underwent DC as a second/third-tier intervention, patient, injury and management variables including physiological monitoring data and administration of thiopental were analysed, as well as Extended Glasgow Outcome score (GOSE) at 6 months. ResultsIn the current cohorts, patients were older than in the surgical RESCUEicp cohort (mean 39.6 vs. 32.3; p < 0.001), had higher Glasgow Motor Score on admission (GMS < 3 in 24.3% vs. 53.0%; p = 0.003) and 37.8% received thiopental (vs. 9.4%; p < 0.001). Other variables were not significantly different. GOSE distribution was: death 24.3%; vegetative 2.7%; lower severe disability 10.8%; upper severe disability 13.5%; lower moderate disability 5.4%; upper moderate disability 2.7%, lower good recovery 35.1%; and upper good recovery 5.4%. The outcome was unfavorable in 51.4% and favorable in 48.6%, as opposed to 72.6% and 27.4% respectively in RESCUEicp (p = 0.02). ConclusionOutcomes in DC patients from two prospective cohorts reflecting everyday practice were better than in RESCUEicp surgical patients. Mortality was similar, but fewer patients remained vegetative or severely disabled and more patients had a good recovery. Although patients were older and injury severity was lower, a potential partial explanation may be in the pragmatic use of DC in combination with other second/third-tier therapies in real-life cohorts. The findings underscore that DC maintains an important role in managing severe TBI.

Omega-3 Polyunsaturated Fatty Acids Protect Neurological Function After Traumatic Brain Injury by Suppressing Microglial Transformation to the Proinflammatory Phenotype and Activating Exosomal NGF/TrkA Signaling.

The transformation of microglia to a pro-inflammatory phenotype at the site of traumatic brain injury (TBI) drives the progression of secondary neurodegeneration and irreversible neurological impairment. Omega-3 polyunsaturated fatty acids (PUFA) have been shown to suppress this phenotype transformation, thereby reducing neuroinflammation following TBI, but the molecular mechanisms are unknown. We found that Omega-3 PUFA suppressed the expression of disintegrin metalloproteinase (ADAM17), the enzyme required to convert tumor necrosis factor-α (TNF-α) to the soluble form, thereby inhibiting the TNF-α/NF-κB pathway both in vitro and in a mouse model of TBI. Omega-3 PUFA also prevented the reactive transformation of microglia and promoted the secretion of microglial exosomes containing nerve growth factor (NGF), activating the neuroprotective NGF/TrkA pathway both in culture and TBI model mice. Moreover, Omega-3 PUFA suppressed the pro-apoptotic NGF/P75NTR pathway at the TBI site and reduced apoptotic neuronal death, brain edema, and disruption of the blood-brain barrier. Finally, Omega-3 PUFA preserved sensory and motor function as assessed by two broad-spectrum test batteries. The beneficial effects of Omega-3 PUFA were blocked by an ADAM17 promotor and by a NGF inhibitor, confirming the pathogenic function of ADAM17 and the central neuroprotective role of NGF. Collectively, these findings provide a strong experimental basis for Omega-3 PUFA as a potential clinical treatment for TBI.

The Role of Cisternostomy in the Management of Severe Traumatic Brain Injury: A Triple-Center Study

Background: Traumatic brain injury (TBI) is a critical public health problem worldwide, constituting a major cause of mortality and morbidity for people of all ages, but especially in the younger population. Decompressive craniectomy (DC) and cisternostomy are surgical procedures commonly used in the management of severe TBI, but their effectiveness in improving outcomes remains controversial. Methods: We conducted a prospective longitudinal study on patients who underwent surgical treatment for severe TBI between 2021 and 2022. The extended Glasgow outcome scale (GOS-E) was used to assess clinical outcome at 2 weeks, 3 months, and 6 months after surgery. Results: The study included 30 patients (21 men and 9 women) who met the inclusion criteria. Among them, 24 patients (80%) underwent DC combined with cisternostomy, while 6 patients (20%) underwent cisternostomy alone. The initial Glasgow Coma Scale (GCS) score at admission ranged from 4 to 8 points, with an average score of 5.9. The overall mortality and overall morbidity was 13.3% and 20%, respectively. The mortality rate was 12.5% and 16.7% in the DC + cisternostomy group and in the cisternostomy alone group, respectively. No statistically significant difference was seen between the two groups in terms of mortality, morbidity and favorable outcome at 2 weeks, 3 months and 6 months. Conclusions: Our preliminary multi-center study shows a good clinical outcome in patients who underwent DC + cisternostomy or cisternostomy alone in both early and long-term follow-up. Larger multi-center randomized trials are needed to establish the effectiveness of cisternostomy in the management of TBI.

The Effect ofConcussion Mechanism ofInjury onSleep Problems inActive Duty Service Members Following Deployment.

Sleep disruption is pervasive in the military and is generally exacerbated during deployment, partially due to increases in operational tempo and exposure to stressors and/or trauma. In particular, sleep disruption is a commonly reported symptom following deployment-related traumatic brain injury (TBI), though less is known about the prevalence of sleep disturbance as a function of whether the TBI was induced by high-level blast (HLB) or direct impact to the head. TBI assessment, treatment, and prognosis are further complicated by comorbidity with posttraumatic stress disorder (PTSD), depression, and alcohol misuse. Here, we examine whether concussion mechanism of injury is associated with differences in the prevalence of self-reported sleep disturbance following deployment in a large sample of U.S. Marines while accounting for probable PTSD, depression, and alcohol misuse. This was a retrospective cohort study of active duty enlisted Marines with a probable concussion (N = 5757) who completed the Post-Deployment Health Assessment between 2008 and 2012. Probable concussion was defined as endorsement of a potentially concussive event with corresponding loss or alteration of consciousness. The presence of concussion-related sleep problems was assessed with a dichotomous item. Probable PTSD, depression, and alcohol misuse were assessed using the Primary Care PTSD Screen, the Patient Health Questionnaire-2, and the Alcohol Use Identification Test-Concise, respectively. Logistic regression models investigated the effects of mechanism of injury (HLB vs. impact), PTSD, depression, and alcohol misuse on the presence of sleep problems, adjusting for sex and pay grade. The study was approved by the Naval Health Research Center Institutional Review Board. Approximately 41% of individuals with a probable deployment-related concussion reported sleep problems following the event; 79% of concussed individuals reporting both HLB and probable PTSD reported sleep problems. All main effects were significantly associated with sleep disturbance in adjusted models. PTSD showed the strongest association with sleep disturbance (adjusted odds ratio [AOR] = 2.84), followed by depression (AOR = 2.43), HLB exposure (AOR = 2.00), female sex (AOR = 1.63), alcohol misuse (AOR = 1.14), and pay grade (AOR = 1.10). A significant HLB × PTSD interaction emerged (AOR = 1.58), which suggests that sleep disturbance was elevated among those with both HLB-induced (vs. impact-induced) concussions and presence (vs. absence) of PTSD. No other significant interactions emerged. To our knowledge, this is the first study to examine the prevalence of concussion-related sleep complaints following deployment as a function of the mechanism of injury in individuals with and without probable PTSD and depression. Individuals with HLB-induced concussion were twice as likely to report sleep problems as those with an impact-induced concussion. Future work should examine these effects longitudinally with validated measures that assess greater precision of exposure and outcome assessment (e.g., blast intensity and type of sleep disturbance).

A case of intravenous iron administration resulting in cerebral edema expansion

BackgroundIron plays an important role in the development of perihematomal edema (PHE) in the setting of intracerebral hemorrhage (ICH). Cerebral iron is increased via direct hemoglobin release in ICH, and several studies have investigated the use of iron-chelating agents to mitigate its toxicity. However, the effect of systemic iron administration, corroborating the reverse concept, has never been investigated or reported clinically. We report the first case of systemic iron administration in the setting of hemorrhagic traumatic brain injury (TBI).Case presentationA 46-year-old woman was admitted to the hospital with acute moderate-to-severe TBI. Her head computed tomography (CT) scan showed bifrontal hemorrhagic contusions with mild PHE. She was started on hypertonic saline 3% continuous infusion and her condition remained stable initially. She was found to be anemic and was given intravenous iron sucrose. Shortly after iron administration, her mental status declined, and left pupil became dilated and sluggish. Repeat CT demonstrated significantly worsening PHE. This prompted maximum hyperosmolar therapy and external ventricular drain (EVD) placement which both were weaned off slowly due to liable ICPs. She was discharged home after a 25-day hospital stay.ConclusionsWe believe this is the first report of exacerbating PHE accompanied by clinical decline after intravenous iron administration in the setting of acute hemorrhagic brain contusions. Though the effects of systemic iron administration on brain edema and the treatments targeting cerebral iron are poorly understood, the administration of systemic iron in acute TBI seems to be detrimental. More research is needed to address iron toxicity in TBI. Our case adds to the growing evidence for such a pathway in the treatment of ICH and TBI.

Effects of electroacupuncture on neurological function and expressions of p-JNK and Beclin-1 in traumatic brain injury rats

To observe the effect of electroacupuncture (EA) on neurological function, the expressions of phosphorylated c-Jun amino terminal kinase (p-JNK) and Beclin-1 in rats with traumatic brain injury (TBI), so as to explore the underlying mechanism of EA in the treatment of TBI. A total of 64 SD rats were randomly divided into blank, sham, modeling groups, with 8 rats in the blank group and the sham group and 48 rats in the modeling group. The modified Feeney free-fall impact method was used to establish the TBI rat model. After modeling, rats of the modeling group were randomly divided into model and EA groups, which were further divided into 3 d, 7 d and 14 d subgroups with 8 rats in each group. Rats in the EA group were treated with acupuncture at "Baihui" (GV20, retained for 15 min), "Shuigou" (GV26, stabbed for 20 s), "Neiguan" (PC6) and "Zusanli" (ST36) of the right side. EA (2 Hz, 1 mA) was applied to PC6 and ST36 for 15 min. The above treatments were performed once a day, and different subgroups were continuously stimulated for 3, 7 and 14 days, respectively. The neurological impairment was evaluated by modified neurological severity score(mNSS). The pathological morphological changes and the protein expressions of p-JNK and Beclin-1 in the injured area of the brain were detected by Nissl staining and immunohistochemistry, separately. After modeling, the mNSS and the protein expressions of p-JNK and Beclin-1 were increased (P< 0.05) on day 3, 7 and 14 in the model group relative to the sham group. The Nissl bodies were reduced or even dissolved and neurons were seriously damaged in the model group on the 3rd day, which were mildly repaired on day 7 and 14. Following acupuncture interventions, compared with the model group, the mNSS on day 7 and 14 and the protein expressions of p-JNK and Beclin-1 on day 3, 7 and 14 were decreased (P< 0.05)in the EA group. The status of Nissl bodies and neurons in the EA group was better at all time points than that in the model group. There were no significant differences in the above indicators between the blank group and the sham group. EA can significantly improve the neurological function of TBI model rats, which may be related to its effects in down-regulating the protein expressions of p-JNK and Beclin-1 in the injured area of the brain.

LRP1 Deficiency Promotes Mitostasis in Response to Oxidative Stress: Implications for Mitochondrial Targeting after Traumatic Brain Injury.

The brain undergoes oxidative stress and mitochondrial dysfunction following physiological insults such as Traumatic brain injury (TBI), ischemia-reperfusion, and stroke. Pharmacotherapeutics targeting mitochondria (mitoceuticals) against oxidative stress include antioxidants, mild uncouplers, and enhancers of mitochondrial biogenesis, which have been shown to improve pathophysiological outcomes after TBI. However, to date, there is no effective treatment for TBI. Studies have suggested that the deletion of LDL receptor-related protein 1 (LRP1) in adult neurons or glial cells could be beneficial and promote neuronal health. In this study, we used WT and LRP1 knockout (LKO) mouse embryonic fibroblast cells to examine mitochondrial outcomes following exogenous oxidative stress. Furthermore, we developed a novel technique to measure mitochondrial morphometric dynamics using transgenic mitochondrial reporter mice mtD2g (mitochondrial-specific Dendra2 green) in a TBI model. We found that oxidative stress increased the quantity of fragmented and spherical-shaped mitochondria in the injury core of the ipsilateral cortex following TBI, whereas rod-like elongated mitochondria were seen in the corresponding contralateral cortex. Critically, LRP1 deficiency significantly decreased mitochondrial fragmentation, preserving mitochondrial function and cell growth following exogenous oxidative stress. Collectively, our results show that targeting LRP1 to improve mitochondrial function is a potential pharmacotherapeutic strategy against oxidative damage in TBI and other neurodegenerative diseases.

Non-Invasive Vagus Nerve Stimulation Improves Brain Lesion Volume and Neurobehavioral Outcomes in a Rat Model of Traumatic Brain Injury.

Abstract Traumatic brain injury (TBI) continues to be a major cause of death and disability worldwide. This study assessed the effectiveness of non-invasive vagus nerve stimulation (nVNS) in reducing brain lesion volume and improving neurobehavioral performance in a rat model of TBI. Animals were randomized into three experimental groups: (1) TBI with sham stimulation treatment (Control), (2) TBI treated with five lower doses (2-min) nVNS, and (3) TBI treated with five higher doses (2 × 2-min) nVNS. We used the gammaCore nVNS device to deliver stimulations. Magnetic resonance imaging studies were performed 1 and 7 days post-injury to confirm lesion volume. We observed smaller brain lesion volume in the lower dose nVNS group compared with the control group on days 1 and 7. The lesion volume for the higher dose nVNS group was significantly smaller than either the lower dose nVNS or the control groups on days 1 and 7 post-injury. The apparent diffusion coefficient differences between the ipsilateral and contralateral hemispheres on day 1 were significantly smaller for the higher dose (2 × 2 min) nVNS group than for the control group. Voxel-based morphometry analysis revealed an increase in the ipsilateral cortical volume in the control group caused by tissue deformation and swelling. On day 1, these abnormal volume changes were 13% and 55% smaller in the lower dose and higher dose nVNS groups, respectively, compared with the control group. By day 7, nVNS dampened cortical volume loss by 35% and 89% in the lower dose and higher dose nVNS groups, respectively, compared with the control group. Rotarod, beam walking, and anxiety performances were significantly improved in the higher-dose nVNS group on day 1 compared with the control group. The anxiety indices were also improved on day 7 post-injury compared with the control and the lower-dose nVNS groups. In conclusion, the higher dose nVNS (five 2 × 2-min stimulations) reduced brain lesion volume to a level that further refined the role of nVNS therapy for the acute treatment of TBI. Should nVNS prove effective in additional pre-clinical TBI models and later in clinical settings, it would have an enormous impact on the clinical practice of TBI in both civilian and military settings, as it can easily be adopted into routine clinical practice.

Alpha-methyltyrosine reduces the acute cardiovascular and behavioral sequelae in a murine model of traumatic brain injury.

Increased catecholamines contribute to heightened cardiovascular reactivity and behavioral deficits after traumatic brain injury (TBI); adrenergic receptor blockade has limited success in reducing adverse sequelae of TBI. Injury-induced increases in the synthesis of catecholamines could contribute to adverse outcomes in TBI. Inhibition of catecholamine synthesis with alpha-methyltyrosine (αMT) could offer a benefit after TBI. Original research trial in mice randomized to αMT (50 mg·kg -1 ·d -1 ) or vehicle for 1 week after TBI induced by controlled cortical impact. Primary outcomes of cardiovascular reactivity and behavioral deficits were assessed after 1 week. Secondary outcomes included blood brain barrier permeability and quantification of gene transcription whose products determine intraneuronal chloride concentrations, the release of catecholamines, and activation of the sympathetic nervous system. These genes were the alpha-2 adrenergic receptor ("Adra2c"), the sodium-potassium-chloride cotransporter ("Nkcc1"), and the potassium chloride cotransporter ("Kcc2"). We also assessed the effect of TBI and αMT on the neuronal chloride/bicarbonate exchanger ("Ae3"). Traumatic brain injury-induced increases in blood pressure and cardiac reactivity were blocked by αMT. Inhibition of catecholamine synthesis decreased blood brain barrier leakage and improved behavioral outcomes after TBI. Traumatic brain injury diminished the transcription of Adra2c and enhanced expression of Nkcc1 while reducing Kcc2 transcription; αMT prevented the induction of the Nkcc1 by TBI without reversing the effects of TBI on Kcc2 expression; αMT also diminished Ae3 transcription. Traumatic brain injury acutely increases cardiovascular reactivity and induces behavioral deficits in an αMT-sensitive manner, most likely by inducing Nkcc1 gene transcription. Alpha-methyltyrosine may prove salutary in the treatment of TBI by attenuating the enhanced expression of Nkcc1, minimizing blood brain barrier leakage, and diminishing central catecholamine and sympathetic output. We also found an unreported relationship between Kcc2 and the chloride/bicarbonate exchanger, which should be considered in the design of trials planned to manipulate central intraneuronal chloride concentrations following acute brain injury.

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.