Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury

Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.

Changes of Nitric Oxide and Its Relationship with Clinical Features,Intracranial Pressure and Outcome in Acute Head Injury

To investigate the content and dynamics of nitric oxide (NO) in the cerebrospinal fluid (CSF) of patients with acute head injury and to clarify the relationship of NO with clinical features and intracranial pressure (ICP) as well as outcomes, 38 adults with acute head injury were studied. Glasgow Coma Scale (GCS) obtained at admission and Glasgow Outcome Scale (GOS) 3 months after injury was assessed. ICP was surveyed via intraventricular catheter and lumbar puncture and CSF samples were obtained simultaneously. NO was determined with Griess reagents. Results showed that NO peak content in the head injury group was significantly higher than that of the control group. During dynamic research, no peak content of mildly injured cases and severely injured ones appeared in different time windows respectively. The peak value of NO was distinctly higher in the severe group than in the mild group. NO peak value of the raised ICP group was remarkably higher than that of the normal ICP group. The peak value of NO was considerately higher in the poor outcome group than in the good outcome group. When the content of NO was over 6. 5 μmol/L, the rate of poor outcome was increased. There existed a correlation between NO and GCS, ICP and GOS. It is concluded that the content of NO was increased in patients with acute head injury and the changes of NO had different time windows in severely injured patients and mildly injured ones. The more sever the injury, the higher the NO content; and the more serious the secondary brain injury and brain edema, the worse the outcomes. When NO is combined with GCS, GOS and ICP, it increases the accuracy of judgement to the degree of head injury and outcome.

Risk factors of posttraumatic cerebral infarction in patients with severe and extremely severe head injury

Objective To explore pathogenesis and risk factors for posttraumatic cerebral infarction (PTCI) in patients with severe and extremely severe head injuries for the purpose of providing clues for reducing occurrence of PTCI and case-fatality. Methods Gender,age,Glasgow coma scale (GCS) ,the presence or absence of basicranial fracture,cerebral hernia or infection,surgical modality,hypotension,and the use of diuretics

Knowledge, Attitude, and Practice of Using Helmets in Children amongst Parents to Prevent Head Injuries: A Cross-Sectional Study in Riyadh, Saudi Arabia

Objectives: The primary objective was to characterize the range of Knowledge, Attitude, and Practice (KAP) of Helmet use in children amongst parents to prevent head injuries and death. Methods: This is a cross-sectional study, done by online survey using a snowball sampling technique, the number of included responses were 386 parents (Male and female) living in Riyadh Aged 21 - 60 years old or above. Results: The study showed that there is a difference in Parents’ belief in the importance of helmet use while riding a Bicycle vs Motorcycle/Quad bike and that was affected by parents’ education level, almost all the people who answered the survey (76.7%) agree that it is important for their children to wear a helmet when riding both a Bicycle and a Motorcycle or Quadbike with a cumulative percentage of (93.8%). And almost all agreed on multiple approaches to help increase helmet use be it by forcing rental shops to give out helmets, forcing sellers to recommend the use of helmets, increasing awareness campaigns, and imposing fines for not wearing helmets. Conclusions: This study is the first to explore Family helmet use while riding Bicycles and Motorcycles/Quad bikes. Although Parent’s belief in the importance of helmet use for their children was high, it is clear that the level of practice is low. With that the risk of head injuries might be high, our findings suggest that safety interventions for increasing pediatric helmet use are needed to increase helmet use and reduce the risk of head injury and hospitalization.

dl-3-n-butylphthalide reduces brain damage in mice with closed head injury

To investigate the protective effect of dl 3 n butylphthalide (NBP) as an anti cerebral ischemic drug on brain damage 24?h after closed head injury in mice Methods Closed head injury was induced by dropping a 50 g weight from a height of 18?cm on a metal impounder resting on the parietal bone in mice Results The neurotraumatic model induced impair^ment of memory function, significant cerebral edema, and disruption of the blood brain barrier dl 3 n butylphthalide (50?mg·kg 1 ) given intraperitoneally 5 minutes and 60 minutes after the onset of closed head injury was found to attenuate the impairment of memory function ( P <0 05), alleviate brain edema in the injured cerebral cortex ( P <0 05), and reduce extravasation of plasma protein bound to Evans blue dye by 63 5% ( P <0 01) NBP was also shown to increase the activity of choline acetyltransferase in the injured cortex to 0 83±0 21?ng·min 1 ·mg 1 ( P <0 01, compared with 0 48±0 14?ng·min 1 ·mg 1 of vehicle group) Conclusion NBP provides therapeutic response in experimental closed head injury

Development of a symptom expectation questionnaire for minor head injury

Background and objective:Expectations and beliefs are important predictors of outcome following minor head injury.In this paper,the primary purpose is to develop a simple symptom expectation questionnaire for minor head injury for use in future research studies.Methods:An existing database of 179 injury-naive subjects who completed a 56-item checklist of expected symptoms for minor head injury was analyzed to determine which items could correctly identify an a priori case definition of an expecter (a subject who expected at least one of these symptoms would remain chronic following minor head injury).A total of six of the 56 items were found to be discriminatory,and these were tested in additional subject groups against the original questionnaire.Results:From the original database of 179 subjects completing a 56-item symptom expectation checklist,135 expected that at least one of the 56 symptoms would be chronic following minor head injury.The 135 expecters,however,all chose at least one of six items:headache,anxious or worried,depressed,difficulty concentrating,dizziness,and neck pain.Using these six items,in two new groups of subjects,all those who endorsed one of the 56 symptoms as likely to be chronic following minor head injury (expecters) could also be identified on the 6-item checklist.Conclusions:A shortened (6-item) symptom expectation checklist of commonly reported symptoms following minor head injury (headache,anxious or worried,depressed,difficulty concentrating,dizziness,and neck pain) correctly identifies subjects who expect that at least one symptom will be chronic following minor head injury (i.e.,an expecter).

Rational design of secondary operation for penetrating head injury:A case report

Penetrating head injury is rare,and thus management of such injuries is non-standard.Early diagnosis and intraoperative comprehensive exploration are necessary considering the complexity and severity of the trauma.However,because of the lack of microsurgical techniques in local hospitals,the possible retained foreign bodies and other postoperative complications such as cerebrospinal fluid(CSF)leak usually require a rational design for a secondary operation to deal with.We present a case of a 15-year-old boy who was stabbed with a bamboo stick in his left eye.The chopsticks passed through the orbit roof and penetrated the skull base.In subsequent days,the patient sustained CSF leak and intracranial infection after an unsatisfied primary treatment in the local hospital and had to request a secondary operation in our department.Computed tomography including plain scan,three dimension recon-struction and computed tomographic angiography are used to determine the course and extent of head injury.A frontal craniotomy was performed.Three pieces of stick were found residual and removed with the comminuted orbit bone fragments.A pedicled temporalis muscle fascia graft was applied to repair the frontier skull base and a free temporalis muscle flap to seal the frontal sinus defect.Aggressive broad-spectrum antibiotics of vancomycin and meropenem were administrated for persistent fever after operation.CSF external drainage system continued for 12 days,and was removed 10 days after tem-perature returned to normal.The Glasgow coma scale score was improved to 15 at postoperative day 7 and the patient was discharged at day 22 uneventfully.We believe that appropriate preoperative surgical plan and thorough surgical exploration by microsurgery is essential for attaining a favorable outcome,especially in secondary operation.Good postoperative recovery depends on successfully management before and after operation for possible complications as well.

Chronic subdural haematoma during the COVID-19 lockdown period:late presentation with a longer interval from the initial head injury to the final presentation and diagnosis

Background:The COVID-19 novel coronavirus is contagious,and the mortality is higher in the elderly population.Lockdown in different parts of the world has been imposed since January 2020.Chronic subdural haematoma (cSDH) has a unique natural history in which symptoms can be non-specific,and the onset is insidious.This study aims to evaluate the impact of the COVID-19 pandemic on the presentation of cSDH.Methods:Consecutive adult cSDH patients admitted from 1 March 2020 to 30 April 2020 were reviewed.Exclusion criteria including those who had no definite history of head injury or the diagnosis of cSDH were made from a scheduled follow-up scan.Corresponding data during the same period in 2019 were reviewed for comparison.The primary outcome was the interval between the initial head injury and the final radiological diagnosis of cSDH.Secondary outcomes include Markwalder chronic subdural haematoma grade upon admission,length of stay in the acute hospital,and the modified Rankin scale (mRS) upon discharge.Results:For the primary outcome,the average interval between head injury and the diagnosis of cSDH was significantly longer at 56.6 days (49 to 74 days,SD 9.83 days) during the period from March to April 2020,versus 29.4 days (17 to 42 days,SD 8.59 days) in 2019 for the corresponding period (p = 0.00703).There was no significant difference in the functional outcome upon discharge.Conclusions:cSDH patients can present late during the COVID-19 lockdown period.The functional outcome was comparable when operations for drainage were timely performed.

Clinical studies on diffuse axonal injury in patients with severe closed head injury

OBJECTIVE: To discuss the clinical criteria for diagnosing diffuse axonal injury (DAI). METHODS: Clinical and computed tomographic features of 117 patients with severe closed head injury were analyzed. The authors preliminarily put forward CT diagnostic criteria of DAI, that is, 1) single or multiple small intraparenchymal hemorrhages in the cerebral hemispheres (

BRAIN INJURY BIOMECHANICS IN REAL WORLD VEHICLE ACCIDENT USING MATHEMATICAL MODELS

This paper aims at investigating brain injury mechanisms and predicting head injuries in real world accidents. For this purpose, a 3D human head finite element model （HBM-head） was developed based on head-brain anatomy. The HBM head model was validated with two experimental tests. Then the head finite element（FE） model and a multi-body system （MBS） model were used to carry out reconstructions of real world vehicle-pedestrian accidents and brain injuries. The MBS models were used for calculating the head impact conditions in vehicle impacts. The HBM-head model was used for calculating the injury related physical parameters, such as intracranial pressure, stress, and strain. The calculated intracranial pressure and strain distribution were correlated with the injury outcomes observed from accidents. It is shown that this model can predict the intracranial biomechanical response and calculate the injury related physical parameters. The head FE model has good biofidelity and will be a valuable tool for the study of injury mechanisms and the tolerance level of the brain.

About an Observation of a Child Penetrating Brain Injury by Knife

Background: Reported cases of knife injuries to the head in children are rare. Here we describe a case of pediatric penetrating brain injury by knife (PPBIK) and review literature. The patient’s parents were informed that non-identifying information from the case would be submitted for publication, and they provided consent. Case Presentation: A 3-year-old boy presented to our emergency department with a knife penetrating the front of his head during play. Neurologic examination was normal. Radiograph in lateral view demonstrated a metallic knife entering frontal bone. Computed tomography (CT) scan showed small hemorrhage around the foreign body recognized, accompanied by small pneumocephalus. The knife was surgically removed and the dura was closed. He was discharged home after the surgery with normal neurological status. Conclusion: Only four cases of PPBIK have been reported in the literature. The adequate management of these types of injuries requires a correct neuroradiological evaluation.

The occurrence of diffuse axonal injury in the brain:associated with the accumulation and clearance of myelin debris

The accumulation of myelin debris may be a major contributor to the inlfammatory response after diffuse axonal injury. In this study, we examined the accumulation and clearance of myelin debris in a rat model of diffuse axonal injury. Oil Red O staining was performed on sections from the cerebral cortex, hippocampus and brain stem to identify the myelin debris. Seven days after diffuse axonal injury, many Oil Red O-stained particles were observed in the cerebral cortex, hippocampus and brain stem. In the cerebral cortex and hippocampus, the amount of myelin debris peaked at 14 days after injury, and decreased signiifcantly at 28 days. In the brain stem, the amount of myelin debris peaked at 7 days after injury, and decreased signiifcantly at 14 and 28 days. In the cortex and hippocampus, some myelin debris could still be observed at 28 days after diffuse axonal injury. Our ifndings suggest that myelin debris may persist in the rat central ner-vous system after diffuse axonal injury, which would hinder recovery.

Stability of rat models of fluid percussion-induced traumatic brain injury: comparison of three different impact forces

Fluid percussion-induced traumatic brain injury models have been widely used in experimental research for years. In an experiment, the stability of impaction is inevitably affected by factors such as the appearance of liquid spikes. Management of impact pressure is a crucial factor that determines the stability of these models, and direction of impact control is another basic element. To improve experimental stability, we calculated a pressure curve by generating repeated impacts using a fluid percussion device at different pendulum angles. A stereotactic frame was used to control the direction of impact. We produced stable and reproducible models, including mild, moderate, and severe traumatic brain injury, using the MODEL01-B device at pendulum angles of 6°, 11° and 13°, with corresponding impact force values of 1.0 ± 0.11 atm（101.32 ± 11.16 k Pa）, 2.6 ± 0.16 atm（263.44 ± 16.21 k Pa）, and 3.6 ± 0.16 atm（364.77 ± 16.21 k Pa）, respectively. Behavioral tests, hematoxylin-eosin staining, and magnetic resonance imaging revealed that models for different degrees of injury were consistent with the clinical properties of mild, moderate, and severe craniocerebral injuries. Using this method, we established fluid percussion models for different degrees of injury and stabilized pathological features based on precise power and direction control.

RXPERIMENTAL AND CLINICAL STUDY OF CREATINE KINASE BB ACTIVITY FOR THE DIAGNOSIS ON BRAIN DAMAGE

Objective To study the differential diagnosis on cerebral concussion and mild cerebral contusion value of the brain type creatine kinase isoenzyme(CK BB),and evaluate the seriousness of brain damage and prognosis of the patients with acute head injury.Methods Chromatographic separating and fluorometric quantifying technique was used to detect the CK BB activity in the cerebrospinal fluid(CSF) of 117 patients with acute head injury and 12 patients with increased intracranial pressure and 20 normal people.Results The CSF CK BB activity of the patients with acute head injury was remarkably higher than that of the normal people and the CSF CK BB activity increased with the seriousness of brain damage.There was a close relationship between CSF CK BB activity and prognosis,and higher activity of CSF CK BB indicated poor prognosis.Conclusion CSF CK BB activity could be used as a new index to diagnose brain damage and evaluate the seriousness of brain damage and prognosis.

颈部闭合性创伤致甲状软骨断裂1例

1临床资料患者,男,53岁,因车祸伤1 h于2018-02-13被送至我院急诊科就诊。就诊前患者骑自行车与货车相撞,出现头昏、头痛及吞咽痛,无胸腹痛、无咯血、无呼吸困难,神志清楚,既往有高血压和糖尿病病史。急诊头部CT提示蛛网膜下腔出血,神经外科会诊评估后认为出血量少,无手术指征,建议留急诊科治疗。因患者吞咽痛,请耳鼻咽喉科会诊,查体咽部无水肿、颈部无皮肤裂伤、无肿胀,患者呼吸平稳,无声嘶,无吸气性呼吸困难。喉部因患者体位受限.

Rhubarb extracts in treating complications of severe cerebral injury

Objective To investigate the therapeutic effects of the Chinese medicinal herb, Rhubarb, on severe brain injury Methods Rhubarb extracts in ethyl alcohol and water were used to treat 20 patients with severe cerebral injury complicated by hyperthermia, renal failure, hemorrhage in the upper digestive tract, and increased intracranial pressure Vital signs, variations of Glasgow coma scale (GCS) and intracranial pressure (ICP) of the patients were observed The degree of hemorrhage in the digestive tract and the change in creatinine value were also observed Other 20 patients served as controls Results The result of the treatment group was more marked than that of the control group Three days after administration of the rhubarb extract, the body temperature decreased by 1 1℃, ICP by 0 4?kPa (1?mm?Hg=0 1333?kPa) on average, and the incidence of hemorrhage in the digestive tract by 30% The volume of hemorrhage of the digestive tract decreased by 700±250?ml, and the time for turning occult blood to negative by 10% Conclusion The Chinese medical herb, rhubarb, has multiple therapeutic effects on severe brain injury

Friction Effects in Pedestrian Headform Impacts with Engine Hoods

In the pedestrian headform impact test mandated by the European pedestrian safety requirements the contact friction between the headform and the engine hood affects the headform kinematics and head injury criterion （HIC） to some extent. This study shows that the friction effect is more significant with child headform impact than with adult headform impact and the relative angle between the headform impact direction and the hood surface greatly affects the headform impact sensitivity to the friction coefficient. The sensitivity of the headform kinematics to the friction coefficient is also analyzed. The results show that ac- curate friction coefficients are needed to improve predictions of pedestrian headform impacts with hoods.

Investigating the Head Impact Force-Induced Evolution of Hyperphosphorylated Tau Proteins in Brain Tissue Through Mechanical Mesoscale Finite Element Simulation

For human heads that experienced repetitive subconcussive impacts,abnormal accumulation of hyperphosphorylated tau(p-tau)proteins was found in the postmortem brain tissue.To numerically understand the cause–effect relationship between the external force and the microscopic volume change of the p-tau protein,we created a mesoscale finite element model of the multilayer brain tissue containing microscopic voids representing the p-tau proteins.The model was applied under the loading boundary conditions obtained from a larger length scale simulation.A formerly developed internal state variable elastoplasticity model was implemented to describe the constitutive behaviors of gray and white matters,while the cerebrospinal fluid was assumed to be purely elastic.The effects of the initial sizes and distances of p-tau proteins located at four different brain regions(frontal,parietal,temporal and occipital lobes)on their volumetric evolutions were studied.It is concluded that both the initial sizes and distances of the proteins have more or less(depending on the specific brain region)influential effects on the growth or contraction rate of the p-tau protein.The p-tau proteins located within the brain tissue at the frontal and occipital lobes are more heavily affected by the frontal impact load compared with those at the parietal and temporal lobes.In summary,the modeling approach presented in this paper provides a strategy for mechanically studying the evolution of p-tau proteins in the brain tissue and gives insight into understanding the correlation between macroscopic force and microstructure change of the brain tissue.

Trans-base and trans-vault low-velocity penetrating brain injury:A retrospective comparative study of characteristics,treatment,and outcomes

Low-velocity penetrating brain injury(LVPBI)caused by foreign bodies can pose life-threatening emergencies.Their complexity and lack of validated classification data have prevented standardization of clinical management.We aimed to compare the trans-base and trans-vault phenotypes of LVPBI to help provide guidance for clinical decision-making of such injury type.;A retrospective study on LVPBI patients managed at our institution from November 2013 to March 2020 was conducted.We included LVPBI patients admitted for the first time for surgery,and excluded those with multiple injuries,gunshot wounds,pregnancy,severe blunt head trauma,etc.Patients were categorized into trans-base and trans-vault LVPBI groups based on the penetration pathway.Discharged patients were followed up by outpatient visit or telephone.The data were entered into the Electronic Medical Record system by clinicians,and subsequently derived by researchers.The demography and injury characteristics,treatment protocols,complications,and outcomes were analyzed and compared between the two groups.A t-test was used for analysis of normally distributed data,and a Mann-Whitney U test for non-parametric data.A generalized linear model was further established to determine whether the factors length of stay and performance scale score were influenced by each factor.;A total of 27 LVPBI patients were included in this analysis,comprised of 13(48.1%)trans-base cases and 14(51.9%)trans-vault cases.Statistical analyses suggested that trans-base LVPBI was correlated with deeper wounds;while the trans-vault phenotype was correlated with injury by metal foreign bodies.There was no difference in Glasgow Coma Scale score and the risk of intracranial hemorrhage between the two groups.Surgical approaches in the trans-base LVPBI group included subfrontal(n=5,38.5%),subtemporal(n=5,38.5%),lateral fissure(n=2,15.4%),and distal lateral(n=1,7.7%).All patients in the trans-vault group underwent a brain convex approach using the foreign body as reference(n=14,100%).Moreover,the two groups differed in application prerequisites for intracranial pressure monitoring and vessel-related treatment.Trans-base LVPBI was associated with higher rates of cranial nerve and major vessel injuries;in contrast,trans-vault LVPBI was associated with lower functional outcome scores.;Our findings suggest that trans-base and trans-vault LVPBIs differ in terms of characteristics,treatment,and outcomes.Further understanding of these differences may help guide clinical decisions and contribute to a better management of LVPBIs.

Clinical analysis on 149 old patients with craniocerebral injury

To study the clinical features of craniocerebral injury (CI) in the aged. Methods: The data of 149 old patients with CI hospitalized in the department from July 1991 to May 2000 were studied retrospectively in this study. The causes of injury, traumatic pathology, clinical manifestation and causes of death were analyzed, too. Results: Automobiles were the main victim makers, and falls were the second. And there was no significant difference between the first two kinds of victim makers. The patients suffered mainly from cerebral contusion, intracerebral hematomas and subdural hematomas, and relatively fewer from epidural hematomas. The scores of Glasgow Coma Scale (GCS) were related closely to the prognosis when hospitalized or before surgical treatment. The total mortality rate was 37.5 % in this study. The main cause of death was brain injury. Conclusions: The old patients with CI have a high mortality rate. And the causes of injury, traumatic pathology and clinical manifestation are peculiar in the aged.