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.

Induced neural stem cells regulate microglial activation through Akt-mediated upregulation of CXCR4 and Crry in a mouse model of closed head injury

Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological recovery.However,the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear.In this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 expression.However,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial activation.In agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury mice.Notably,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head injury.In conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neural stem cells on microglial activation via upregulation of CXCR4 and Crry,thereby promoting induced neural stem cell–mediated improvement of neuronal injury,cerebral edema,and neurological disorders following closed head injury.

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.

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.

Early enteral nutrition supplemented with probiotics improved the clinical outcomesin patients with severe head injury： protocol for a meta-analysis of randomizedcontrolled trials

Objective： The aim of this systematic review of randomized controlled trials （RCTs） is to determine the effects of earlyenteral nutrition supplemented with probiotics on clinical outcomes in patients with SHI.Methods and analysis： A systematic search will be carried out in PubMed, Cochrane Central Register of ControlledTrials （CENTRAL）, China National Knowledge Infrastructure （CNKI）, WanFang database, and Chinese BiomedicalLiterature （CBM） in order to identify the randomized controlled trials （RCTs） investigated the potential of early enteralnutrition supplemented with probiotics on patients with severe head injury, as well as we will also manually check thebibliographies of eligible studies and topic-related reviews. We will assign two investigators to independently search allpotential citations, extracted data, and appraised risk of bias accordingly, and then STATA software version 12.0 will beused to statistically analyze all data.Ethics and dissemination： The ethics approval and patient written informed consent will not be required because allanalyses in the present study will be performed based on data from published studies. We will submit our systematicreview to a peer-reviewed scientific journal for publication.

An experimental and clinical study on TXA_2 and PGI_2 content after head injury

The correlation of secondary brain injury with thromboxane A_2(TXA_2) and prostacy- clin (PGI_2) levels following head injury was studied in rats and patients.Thromboxane B_2 (TXB_2) and 6-keto-PGF_(1α) in rat brain homogenate and TXB_2 in cerebral spinal fluid (CSF) of patients with severe head injury were determined by RIA.The effects of ligustrazini hydrochlo- rioi were also tested.The results showed that the concentration of TXB_2 and 6-keto-PGF_(1α) in rat brain was progressively increased within 3h after injury (P<0.01),and the ratio between TXB_2 and 6-keto-PGF_(1α)(T/K value) increased during the early stage after injury,along with the tissue damage aggravation.After the use of ligustrazini hydrochlorioi,TXB_2 content in brain decreased sharply accompanied with a drop in T/K value.Moreover,TXB_2 content in CSF increased within 7 d after injury (P<0.01),and it reached its peak value on the 3rd day. This could indicate that the metabolic imbalance between TXA_2 and PGI_2 might be one of the important factors in the development of secondary brain injury,and ligustrazini hydrochlorioi proved to have a protective effect on the brain tissue by normalizing the metabolism of TXA_2 and PGI_2.In addition,the metabolic disorders of TXA_2 in the brain tissue of head injured pa- tients have much to do with the outcome of the patients.

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

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.

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.

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.

A study on the application of diffuse axonal multi-axis general evaluation for braininjury assessment in small overlap barrier crash test

Purpose:Head injury criterion(HIC)companied by a rotation-based metric was widely believed to behelpful for head injury prediction in road traffic accidents.Recently,the Euro-New Car AssessmentProgram utilized a newly developed metric called diffuse axonal multi-axis general evaluation(DAMAGE)to explain test device for human occupant restraint(THOR)head injury,which demonstratedexcellent ability in capturing concussions and diffuse axonal injuries.However,there is still a lack ofcomprehensive understanding regarding the effectiveness of using DAMAGE for Hybrid III 50thpercentile male dummy(H50th)head injury assessment.The objective of this study is to determinewhether the DAMAGE could capture the risk of H50th brain injury during small overlap barrier tests.Methods:To achieve this objective,a total of 24 vehicle crash loading curves were collected as input datafor the multi-body simulation.Two commercially available mathematical dynamic models,namelyH50th and THOR,were utilized to investigate the differences in head injury response.Subsequently,adecision method known as simple additive weighting was employed to establish a comprehensive braininjury metric by incorporating the weighted HIC and either DAMAGE or brain injury criterion.Furthermore,35 sets of vehicle crash test data were used to analyze these brain injury metrics.Results:The rotational displacement of the THOR head is significantly greater than that of the H50thhead.The maximum linear and rotational head accelerations experienced by H50th and THOR modelswere(544.6±341.7)m/s^(2),(2468.2±1309.4)rad/s^(2) and(715.2±332.8)m/s^(2),(3778.7±1660.6)rad/s^(2),respectively.Under the same loading condition during small overlap barrier(SOB)tests,THOR exhibits ahigher risk of head injury compared to the H50th model.It was observed that the overall head injuryresponse during the small overlap left test condition is greater than that during the small overlap righttest.Additionally,an equation was formulated to establish the necessary relationship between theDAMAGE values of THOR and H50th.Conclusion:If H50th rather than THOR is employed as an evaluation tool in SOB crash tests,newlydesigned vehicles are more likely to achieve superior performance scores.According to the current injurycurve for DAMAGE and brain injury criterion,it is highly recommended that HIC along with DAMAGE wasprioritized for brain injury assessment in SOB tests.

Effects of the windshield inclination angle on head/brain injuries in car-to-pedestrian collisions using computational biomechanics models

Car-to-pedestrian collision(CPC)accidents occur frequently,and pedestrians often suffer serious head/brain injuries.One major cause is the primary impact with the windshield.Here,we use an umerical sim ulation method to study the influence of the windshield in-clination angle of a passenger car on pedestrian head/brain injury due to CPC accidents.The range of the windshield inclination angle was set at 24°-50°,with an interval of 2°.The results show that the windshield angle significantly affects the pedestrian kine-matics and exerts different effects on the head injury when evaluating with various head injury criteria.Regarding the head peak linear/rotational acceleration and acceleration-based head injury criterion(HIC)/rotational injury criterion(RIC),the predictions at the secondary impact stage have no clear relationship with the windshield angle(R^(2)=0.04,0.07,0.03 and 0.26,respectively)and their distributions are scattered.In the primary impact,the peak linear acceleration and HIC show a weak trend of first decreasing and then increasing with the increasing of the windshield angle,and the rotational acceleration and RIC tend to remain relatively con-stant.Regarding the cum ulative strain dama ge measure(CSDM)criterion,the predictions at the primary impact are slightly lower than those at the secondary impact,and the trend of first decreasing and then increasing with the increase in the windshield angle is observed at both impact stages.When the windshield inclination angle is approximately 32°-40°,the head injury severity in both impact phases is generally lower than that predicted at other windshield angles.

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.

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 (

Effect of sedative agent selection on morbidity, mortality and length of stay in patients with increase in intracranial pressure

BACKGROUND: To identify the effects of sedative agent selection on morbidity, mortality, and length of stay in patients with suspected increase in intracranial pressure. Recent trends and developments have resulted in changes to medications that were previously utilized as pharmacological adjuncts in the sedation and intubation of patients with suspected increases in intracranial pressure. Medications that were previously considered contraindicated are now being used with increasing regularity without demonstrated safety and effectiveness. The primary objective of this study is to evaluate and compare the use of Ketamine as an induction agent for patients with increased intracranial pressure. The secondary objective was to evaluate and compare the use of Etomidate, Midazolam, and Ketamine in patients with increased intracranial pressure. METHODS: We conducted a retrospective chart review of patients transported to our facility with evidence of intracranial hypertension that were intubated before trauma center arrival. Patients were identifi ed during a 22-month period from January 2014 to October 2015. Goals were to evaluate the impact of sedative agent selection on morbidity, mortality, and length of stay.RESULTS: During the review 148 patients were identifi ed as meeting inclusion criteria, 52 were excluded due to incomplete data. Of those the patients primarily received; Etomidate, Ketamine, and Midazolam. Patients in the Ketamine group were found to have a lower mortality rate after injury stratifi cation. CONCLUSION: Patients with intracranial hypertension should not be excluded from receiving Ketamine during intubation out of concern for worsening outcomes.

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

Effects of nimodipine on changes of endothelin after head injury in rabbits

Objective: To investigate the effects of nimodipine on changes of endothelin after head injury. Methods: Sixty five adult rabbits were randomized into an injury group (IG, n=30), a nimodipine treatment group (NTG, n=30) and a control group (CG, n=5). With their heads unfixed, the animals in IG and NTG were injured in the frontal parietal zone with BIM II bioimpact. Blood samples and brain tissue were collected before and after injury. The endothelin level was measured with RIA. Results: The endothelin level in plasma and brain tissue was significantly increased 24 hours after injury. At the 8th or/and 24th hours postinjury, the endothelin level was significantly lower in NTG than that in IG. Conclusions: Nimodipine can prevent endothelin from elevation and act as a practical endothelin antagonist after head injury clinically.

Effect of mild hypothermia on partial pressure of oxygen in brain tissue and brain temperature in patients with severe head injury

Objective: To study the changes of partial pressure of oxygen in brain tissue ( P btO 2) and brain temperature (BT) in patients in acute phase of severe head injury, and to study the effect of mild hypothermia on P btO 2 and BT. Methods: The P btO 2 and the BT of 18 patients with severe head injury were monitored, and the patients were treated with mild hypothermia within 20 hours after injury. The rectal temperature (RT) of the patients was kept on 31.5- 34.9℃ for 1-7 days ( 57.7 hours± 28.4 hours averagely), simultaneously, the indexes of P btO 2 and BT were monitored for 1-5 days (with an average of 54.8 hours± 27.0 hours). According to Glasgow Outcome Scale (GOS), the prognosis of the patients was evaluated at 6 months after injury. Results: Within 24 hours after severe head injury, the P btO 2 was significantly lower ( 9.6 mm Hg± 6.8 mm Hg, 1 mm Hg= 0.133 kPa) than the normal value (16-40 mm Hg). After treatment of mild hypothermia, the mean P btO 2 increased to 28.7 mm Hg± 8.8 mm Hg during the first 24 hours, and the P btO 2 was still maintained within the range of normal value at 3 days after injury. The BT was higher than the RT in the patients in acute phase of severe head injury, and the difference between the BT and the RT significantly increased after treatment of mild hypothermia. Hyperventilation (the partial pressure of carbon dioxide in artery (P aCO 2)≈25 mm Hg) decreased the high intracranial pressure (ICP) and significantly decreased the P btO 2. Conclusions: This study demonstrates that P ptO 2 and BT monitoring is a safe, reliable and sensitive diagnostic method to follow cerebral oxygenation. It might become an important tool in our treatment regime for patients in the acute phase of severe head injury requiring hypothermia and hyperventilation.

Moderate hypothermia therapy for patients with severe head injury

Objective: To evaluate the effect and safety of early moderate hypothermia therapy (MHT) on patients with head injury by using parallel control test. Methods: Thirty patients with severe head injury within 6 hours after accidents were treated by MHT generally for 4 10 days. The other 30 patients with similar head injury treated routinely were enrolled for a parallel control test. The mortality, morbidity and changes of some neuro functional indexes as Glasgow Coma Scores, and Glasgow Outcome Scale, levels of endothelin and some other factors of neurobiochemistry in blood plasma were observed. Meanwhile, the dynamic monitoring by transcranial Doppler ultrasonography was conducted in these patients. Results: The mortality in MHT group was significantly lower than that in control group. MHT not only reduced endothelin but also increased the brain biochemical factors, which were helpful to the protection of neurons in the early brain ischemia after head injury. Conclusions: Early MHT can help reduce mortality and morbidity in patients with acute head injury.

The influence of traumatic subarachnoid hemorrhage on prognosis of head injury

Objective: To study the influence of traumatic subarachnoid hemorrhage on secondary intracranial damage in GCS 13 15 head injuries and prognosis. Methods: One hundred and twenty eight patients with mild head injury, including 64 with subarachnoid hemorrhage and 64 without subarachnoid hemorrhage, were selected and analyzed according to the changes of their conditions after injury. Results: Intracranial abnormality was found in 14 patients ( 21.87 %) with subarachnoid hemorrhage and only in 4 patients ( 6.25 %) without subarachnoid hemorrhage (P< 0.01 ). In the 14 patients, 4 were given surgical treatment. Mild disability was in 2 patients and 2 completely recovered. The rest were conservatively treated and achieved complete recovery at last. Conclusions: Traumatic subarachnoid hemorrhage, as a factor of intracranial complications in mild head injury should be given much attention. Early drainage of bloody cerebrospinal fluid by lumbar puncture is an effective method for prevention and treatment of complications in mild head injury.