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.

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 (

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.