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.

Distinct proteins in cortex of rats with closed traumatic brain injury detected by a WCX-2 protein chip

BACKGROUND： Mechanical injury can cause the changes of polygene expression spectrum in rat cerebral cortical nerve cells, and then result in the changes of intracellular protein expression. At present, dielectrophoresis is combined with mass spectrum technique to detect the expression of different proteins in rat cortex after brain injury, but the protein chip technique requires further investigation. OBJECTIVE： To analyze the differences of protein expression spectrum in rat cerebral cortex before and after closed traumatic brain injury using WCX-2 protein chip technique. DESIGN： A randomized controlled animal experiment. SETTING： Training Division of the Medical College of Chinese People＇s Armed Police Force. MATERIALS： Seventy-two male SD rats of clean degree, 350 - 450 g, were provided by the Experimental Animal Center, Academy of Military Medical Sciences of Chinese PLA. Urea, trifluoroacetic acid, CHAPS and Tris （Sigma, USA）; WCX-2 （Ciphergen, USA）. Ultra-high speed hypothermia centrifuger （Bechman, USA）; Rotary tissue microtome （Keuca, Germany）; Biochip processor and PBS II-C protein chip reader （Ciphergen, USA）. METHODS： The experiments were carried out in the Institute of Molecular Pathology, Central Laboratory, and Department of Pathology, Medical College of Chinese People＇s Armed Police Force from June 2005 to March 2006. ① Grouping and treatment： The experiments were completed in molecular pathological institute, central laboratory and pathological department. ② The rats were randomly divided into control group （n =12） and brain injury group （n =60）. Marmarou＇s weight-dropping models were duplicated at different time points in the brain injury group. In the control group, the rats were only treated by incising the skin of head top, without fixing the stainless steel hitting backup plate at the vault of skull, and obtain brain cortex for pathological and protein chip research, and they were killed after 24 hours. The rats in the brain injury group were killed at 4, 8, 12, 24 and 48 hours after model establishment. ③ Pathological observation： Longitudinal section was made on cerebral cortex, and sections of 5 μm were prepared, then stained with hematoxylin and eosin （HE）. ④Protein chip analysis： 100 mg cerebral cortex was collected from each rat, and the protein content in sample was detected with Bradford method, meanwhile, WCX-2 protein chip was used to analyze the protein spectrum. The data were automatically collected with Ciphergen proteinchip 3.0 software, and the results were analyzed using Biomarker Wizard software to compare the differences of protein spectrum in rat cortex between the groups. MAIN OUTCOME MEASURES： Results of the pathological observation of cerebral cortex and the protein spectrum analysis. RESULTS：①Pathological changes of cerebral cortex： In the control group, no necrosis and edema was observed. In the brain injury group, injures of different severity occurred at different time points; After 4 hours, focal or scattered red nerve cells could be observed, the size of some cells was increased, cytoplasm was lightly stained, and only nuclear fragments were seen; After 8 hours, the necrotic nerve cells were increased, and the number of nerve cells was reduced, astrocytes （neuronophagia） could be seen in partial cytoplasm; there was small vascular dilatation, and endothelial cell proliferation; interstitial edema, regional rarefaction lightly stained. After 12- 48 hours, the necrotic nerve cells were reduced, and astrocytes proliferated. ② Results of protein spectrum analysis： The WCX-2 experiment found that the expressions of 5 639, 3 212 and 7 536 u proteins in cerebral cortex changed after injury in the brain injury group. The peak intensity of 5 639 u protein in the brain injury group at 8 hours after injury was higher than that in the control group （P 〈 0.05）; The peak intensity of 3 212 u protein in the brain injury group at 48 hours after injury was higher than that in the control group （P 〈 0.05）; The peak intensity of 7 536 u protein at 24 hours after injury was higher than that in the control group （P 〈 0.05）. CONCLUSION： Brain injury can cause the changes of protein expression spectrum in cerebral cortex, it is suggested that brain injury can induce the expression of protein.

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

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 (

Predictive value and applicability of ocular trauma scores and pediatric ocular trauma scores in pediatric globe injuries

AIM: To evaluate the predictive value and applicability of Ocular Trauma Score(OTS) and Pediatric Ocular Trauma Score(POTS) for closed and open globe injuries in the pediatric group.METHODS: A retrospective study of closed and open globe injuries in children age of 0-18-year-old between 2012-2019 was conducted.Medical records were collected,and injuries were classified using Birmingham Eye Trauma Terminology System(BETTS).The predictive value and applicability of both OTS and POTS to final visual acuity(VA) were analyzed.RESULTS: Of 84 patients,59(70.2%) presented with closed globe injuries(CGI) and 25(29.8%) with open globe injuries(OGI).The mean of initial VA was 0.832±0.904 log MAR.OTS and POTS was calculated.Initial VA(P<0.001) and traumatic cataract(P<0.001) were significantly associated with visual outcome,followed by organic/unclean wound (P=0.001),delay of surger y(P=0.001),iris prolapse(P=0.003),and globe rupture(P=0.008).A strong correlation between OTS and POTS and final VA(r=-0.798,P<0.001;r=-0.612,P<0.001) was found.OTS was more applicable in all age group of pediatric and in contrast to POTS,it was designed for 0-15 years old.POTS requires eleven parameters and OTS six parameters.Even though initial VA was not available,we could still calculate into POTS equation.CONCLUSION: OTS and POTS are highly predictive prognostic tools for final VA in CGI and OGI's in children.

Effect of mild head injury on intelligence in Zahedan, Iran

Objective： To investigate the effects of mild head injury （HI） on the victims＇ intelligence by measuring their intelligence quotient （IQ）.Methods： This cohort study was performed in Khatamol-Anbia Hospital, Zahedan, Iran and the IQs of 30 mild HI patients were measured right after the injury （IQ0） and six months later （IQ6）. The IQs of 90 close relatives of the patients were also measured at the same period of time as the non-exposure group. The IQs were measured with Wechsler adult intelligence scale-revised （WAIS-R）. The IQ0, IQ6 and their differences （IQ change） were compared in HI patients and their relatives using the Student＇s t test.Results： The mean IQ0 of the HI patients was similar to their relatives. The IQ6 of HI patients appeared to be less than those of their relatives. Moreover, the IQ6 of the HI patients appeared to be less than their initial scores. HI was associated with more decrease in IQ6 compared with IQ0and the female subjects showed more decrease in IQ6 compared with their IQ0.Conclusion： HI seems to be associated with decrease in IQ six months after the injury and it is more evident in female HI patients.

Forensic medical study on morphology and formative mechanism of blunt head injury

Objective： To study the patterns and morphologic characteristics of blunt head injury and analyse its formative mechanism in attempt to provide references for medicolegal expertise. Methods： The statistical analysis was done in terms of gender, age, as well as the nature, pattern, location, and feature of the injuries. Results： Among the 202 cases of head injury-induced death, 124 were male and 78 female with the age ranging from 1-81 years. Death caused by homicide was dominant （106, 52.5%）, followed by suicide （49, 24.3%） and accident （44, 21.8%）. The majority of suicide-induced death were byfalling from height, and traffic crash was responsible for majority of unexpected death cases. The morphology and pathogenesis of the injuries varied according to differences on the mode, magnitude, and orientation of the outside force giving rise to blunt injury as well as the character of vulnerants. Conclusion： Studies on the morphology and its forma- tive rationale of blunt head injury will offer easy access to medicolegal expertise on the mode and character of the injury.

Morel-Lavallee lesion

Objective To review current knowledge of the Morel-Lavallee lesion （MLL） to help clinicians become familiar with this entity.Familiarization may decrease missed diagnoses and misdiagnoses.It could also help steer the clinician to the proper treatment choice.Data sources A search was performed via PubMed and EMBASE from 1966 to July 2013 using the following keywords：Morel-Lavallee lesion,closed degloving injury,concealed degloving injury,Morel-Lavallee effusion,Morel-Lavallee hematoma,posttraumatic pseudocyst,posttraumatic soft tissue cyst.Study selection Chinese and English language literatures relevant to the subject were collected.Their references were also reviewed.Results Morel-Lavallee lesion is a relatively rare condition involving a closed degloving injury.It is characterized by a filled cystic cavity created by separation of the subcutaneous tissue from the underlying fascia.Apart from the classic location over the region of the greater trochanter,MLLs have been described in other parts of the body.The natural history of MLL has not yet been established.The lesion may decrease in volume,remain stable,enlarge progressively or show a recurrent pattern.Diagnosis of MLL was often missed or delayed.Ultrasonography,computed tomography,and magnetic resonance imaging have great value in the diagnosis of MLL.Treatment of MLL has included compression,local aspiration,open debridement,and sclerodesis.No standard treatment has been established.Conclusions A diagnosis of MLL should be suspected when a soft,fluctuant area of skin or chronic recurrent fluid collection is found in a region exposed to a previous shear injury.Clinicians and radiologists should be aware of both the acute and chronic appearances to make the correct diagnosis.Treatment decisions should base on association with fractures,the condition of the lesion,symptom and desire of the patient.

Epidemiological profile of pediatric ocular trauma in a tertiary hospital of northern India

Purpose： Ocular trauma is one of the most common causes of acquired blindness in children. It measures about 8%-14% of total childhood injuries. This study aims to determine the epidemiological profile of ocular trauma in the pediatric age group attending a tertiary hospital in northern India. Methods： A retrospective study was conducted in our hospital between June 2014 to July 2015 and all the children aged 0-16 years presenting with ocular trauma in eye outpatient department and emergency were enrolled in the study. Various epidemiological parameters like age, sex distribution, duration of presentation, mode of injury, type of injury and final visual outcome were analyzed. Results： Of total 357 patients, 271 （76%） were below the age of 12 years： 41.1% of children with ocular trauma belonged to age group 2-6 years. The male to female ratio was 2.9：1. Out of total patients, 242 （67.8%） presented with closed globe injury. Among the closed globe injury, the history of fall was present in about 35% of children, followed by trauma while playing with bat/ball （15.7%） and finger nail trauma （13.2%）. Among open globe injury, trauma with needle, knife, glass and pen were common causes. Home was the most common place of injury （47.8%）, followed by streets （17.9%） and playground （14.9%）. Conclusion： Children are vulnerable to ocular trauma and need more supervision. Sharp objects like needles, knives, household chemicals like acids should be out of reach of children.