Exploration and thinking of standardized residency training education for the residents in the intensive care unit of neurosurgery department / 中华医学教育探索杂志

Critical neurosurgery is one of the difficulties and key points in the standardized residency training of neurosurgery. Through the systematic and standardized training of the residents of the Intensive Care Unit of Neurosurgery Department in The First Affiliated Hospital of Chongqing Medical University, consisting of first aid skills training, multi-modal case analysis with complementary theory and practice, expansion of neuroimaging and electrophysiological knowledge, specialized knowledge training in surgical operation and perioperative management, and regular case discussion, their clinical thinking becomes more mature, the time to master the management methods of neurosurgical intensive care patients is significantly shortened, the initiative to participate in clinical practice is also significantly increased, and the perioperative management methods of neurosurgical patients are more deeply understood. These trainings have effectively improved the teaching effect of neurosurgery intensive care unit.

Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus disease 2019 (version 2023) / 中华创伤杂志

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Neuroprotective effect of long noncoding RNA-nuclear-enriched abundant transcript 1 on traumatic brain injury in mice and its possible mechanism / 中华创伤杂志

Objective:To explore the impact of the expression of long noncoding RNA-nuclear-enriched abundant transcript 1 (NEAT1) on neurological function and neuronal apoptosis after traumatic brain injury (TBI) in mice and the possible mechanism.Methods:According to the random number table, 90 C57BL/6J mice were divided into sham group, blank control group, empty virus group 1, empty virus group 2, NEAT1 over-expression group and NEAT1 knockdown group, with 15 mice per group. The traumatic brain injury (TBI) was simulated by controlled cortical injury (CCI) model, and NEAT1 was regulated by intracerebroventricular injection with recombinant adenovirus. The neurological severity score (NSS) and Morris water maze test were used to evaluate the neurological function in blank control group, NEAT1 over-expression group and NEAT1 knockdown group within 1 week and 14-21 days after injury. The Western blot was used to observe the expressions of P53-induced protein with a death domain 1 (Pidd1), caspase-2, caspase-9 and caspase-3 in blank control group at 6 hour and 1, 3, 7 days after injury. The TUNEL method and immunofluorescence were used to observe the neurological apoptosis and expression of Pidd1 in blank control group, NEAT1 over-expression group and NEAT1 knockdown group at 3 days after injury. The Western blot analysis was used to detect protein expressions of Pidd1, caspase-2, cytochrome c (Cyt c) and caspase-3 in sham group, blank control group, empty virus groups, NEAT1 over-expression group and NEAT1 knockdown group at 3 days after injury.Results:The NSS was significantly reduced in NEAT1 over-expression group [(3.5±0.7)points], and was significantly increased in NEAT1 knockdown group [(5.0±1.5)points]at day 1 after injury, when compared with blank control group [(4.9±1.0)points]( P<0.01). The Morris water maze test showed that the time to find platform was decreased in NEAT1 over-expression group[(10.9±2.8)seconds], and was prolonged in NEAT1 knockdown group [(30.7±6.2)seconds] at day 19 after injury ( P<0.05 or 0.01), when compared with blank control group [(20.1±5.6)seconds]. The Western blot analysis showed that the expressions of Pidd1, caspase-2, caspase-9 and caspase-3 had significant increase at day 3 after injury ( P<0.01). The TUNEL test showed that the apoptosis rate of neurons was significantly decreased in NEAT1 over-expression group [(18.0±2.7)%], and the apoptosis rate was significantly increased in NEAT1 knockdown group [(63.0±8.6)%] at day 3 after injury ( P<0.01). Immunofluorescence showed that the expression of Pidd1 protein in cytoplasm of the neurons was decreased in NEAT1 over-expression group [(22.7±2.2)%]( P<0.01), and was increased in NEAT1 knockdown group [(72.7±7.0)%]( P<0.01) at day 3 after injury, when compared with blank control group. The Western blot analysis showed that the expressions of Pidd1, capsase-2, Cyt c and caspase-3 were significantly reduced in NEAT1 over-expression group (0.5±0.0, 0.3±0.0, 0.5±0.0, 0.4±0.0) at day 3 after injury, when compared with blank control group. However, the results were opposite in NEAT1 knockdown group. Conclusion:After TBI, the NEAT1 can reduce the activation of caspase-3 through the Pidd1-caspase-2-Cyt c pathway after TBI, regulate neuronal apoptosis, and ultimately play a protective role in neurological function.

The utility of ultrasonography in evaluation and protection of diaphragm function / 中国小儿急救医学

Diaphragm plays an important role in human autonomous breathing.Diaphragm dysfunction is an important cause of respiratory failure and prolonging weaning from mechanical ventilation, which increases the patient′s mortality, and prolongs the time of hospitalization.Therefore, evaluation of diaphragm function is crucial for critically ill patients.In recent years, ultrasonography can quantify the features of the diaphragm under various normal and pathological conditions, as a simple, rapid, non-invasive, non-radiative, and repeatable bedside examination method, which has been used to evaluate diaphragm function.This study was aimed to clarify the research progress and existing problems of application of ultrasound in the evaluation of diaphragm function, and introduce the potential ways and challenges of implementing protective mechanical ventilation of the diaphragm by ultrasound, as well as provide guidance and assistance for the clinical application of this technology.

Blocking ERK signaling pathway lowers MMP-9 expression to alleviate brain edema after traumatic brain injury in rats / 浙江大学学报·医学版

OBJECTIVE@#To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury.@*METHODS@#Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting.@*RESULTS@#Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01).@*CONCLUSIONS@#Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.

Blocking ERK signaling pathway lowers MMP-9 expression to alleviate brain edema after traumatic brain injury in rats / 南方医科大学学报

OBJECTIVE@#To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury.@*METHODS@#Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting.@*RESULTS@#Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01).@*CONCLUSIONS@#Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.

Inspirations to China from the quality control of Germany private hospital—taking Hannover International Neuroscience Institute as an example / 中华医学教育探索杂志

To improve the quality control of private hospital is urgent in China. Through the visiting to International Neuroscience Institute, Hannover, Germany, the author analyzed the advantages of Germany Medical System, and provided several beneficial aspirations for Chinese Medical System Reformation, including sound Medical Insurance System, efficient quality control based on information platform, powerful government and civilian regulator, elastic Salary Administration, and high self-discipline of medical staff.

Effect of long non-coding RNA F19 on secondary brain injury after traumatic brain injury in mice / 中华创伤杂志

Objective To investigate the effect of long non-coding RNA F19 (lncRNA F19) on secondary brain injury following traumatic brain injury (TBI) in mice. Methods (1) A total of 96 C57BL/6J male wild-type mice were divided into sham group, sham+control lentivirus group, sham+F19 lentivirus group, TBI group, TBI+control lentivirus group and TBI+F19 lentivirus group according to the random number table. Each group consisted of two subgroups of 1 day and 3 days after TBI, with eight mice per subgroup. The expression and silence efficiency of lncRNA F19 were detected. ( 2 ) A total of 96 C57BL/6J male wild-type mice were divided into sham group, TBI+control lentivirus group and TBI + F19 lentivirus group according to the random number table. Each group consisted of two subgroups of 1 day and 3 days after TBI, with 16 mice per subgroup. The effect of lncRNA F19 on neuronal apoptosis after TBI was recorded. The mice TBI model was established using the controlled cortical damage method (CCI). The lncRNA F19 lentivirus or control lentivirus were administrated by intracerebroventricular injection 5 days before injury. The expressions of lncRNA F19 ( 2 -ΔΔct ) were detected by real-time quantitative PCR ( qRT-PCR ) at 1 day and 3 days after injury. The Toll-like receptor 4 (TLR4), B lymphocyte tumor-2 (Bcl-2) and Bcl-2 related protein (Bax) expressions were detected by Western blot. The TUNEL was used to detect apoptosis around the traumatic lesions. Results From the first day after injury, both in the sham operation and TBI groups, the control lentivirus had no effect on the level of lncRAN F19 (P >0. 05). One day after injury, compared with sham +control lentivirus group, the levels of lncRNA F19 in sham + F19 lentivirus group were significantly decreased (0. 07 ± 0. 07:0. 93 ± 0. 17);compared with TBI+control lentivirus group, levels of lncRNA F19 in TBI+F19 lentivirus group were significantly decreased (2. 91 ± 1. 18:0. 52 ± 0. 32) (P<0. 05). There were significantly lower protein levels of TLR4 (0. 51 ± 0. 13:0. 66 ± 0. 15), Bax (0. 45 ± 0. 06:0. 67 ± 0. 16), lower TUNEL-positive neurons ratio [(23. 55 ± 6. 85)％ : (31. 58 ± 7. 52)％], but higher protein levels of Bcl-2 (0. 76 ± 0. 16:0. 47 ± 0. 12) in TBI+F19 lentivirus group compared with the TBI+ control lentivirus group (P <0.05). Three days after injury, compared with sham + control lentivirus group, levels of lncRNA F19 in sham+F19 lentivirus group were significantly decreased (0. 11 ± 0. 09:0. 96 ± 0. 09); compared with TBI+control lentivirus group, levels of lncRNA F19 in TBI+F19 lentivirus group were significantly decreased (0. 54 ± 0. 24:3. 39 ± 0. 90) (P <0. 05). There were significantly lower protein levels of TLR4 (0. 60 ± 0. 20):(0. 85 ± 0. 09)], lower Bax (0. 60 ± 0. 12:0. 88 ±0. 21), lower TUNEL-positive neurons ratio [(29. 10 ± 7. 37)％ :(39. 22 ± 10. 64)％], but higher protein levels of Bcl-2 (0. 66 ± 0. 12:0. 35 ± 0. 16) in TBI+F19 lentivirus group compared with the TBI+control lentivirus group (P<0. 05). Conclusion Inhibition of lncRNA F19 can significantly reduce the TLR4-induced neuronal apoptosis in cortex after TBI in mice and alleviate reduce the secondary brain injury.

Expression profile of circular RNA in mouse cortex after subarachnoid hemorrhage / 中华神经医学杂志

Objective To explore the altered expression of circular RNA (circRNA) and mRNA in the mouse cortex in the early phase of subarachnoid hemorrhage (SAH) and possible biological functions of the circRNA in early brain injury (EBI).Methods A total of 18 C57BL/6J male mice were randomly divided into a sham and a SAH group (n=9).SAH models were prepared by endovascular perforation.Total RNAs of brain samples were extracted to construct the cDNA library 24 h after operation.RNA-sequencing (RNA-seq) was carried out by HiSeqTM 2500 User Guide and followed by RT-qPCR for confirmation.Reads were aligned to the mouse transcriptome to obtain expression profiles ofcircRNA and mRNA.Bioinformatic study included GO analysis,KEGG pathway analysis and forecast of targeted miRNA of circRNA.Results A total of 26 circRNA (6 up-regulated and 20 down-regulated) and 804 mRNA (396 up-regulated and 408 down-regulated) were significantly changed.These altered mRNA were mainly related to regulation of neuronal synaptic plasticity,inflammatory and immune response.Bioinformatics showed that some significantly altered circRNA contained binding sites for many miRNA.The RT-qPCR analysis of 4 randomly selected circRNA (circFoxj3,circSetbp1,circArpp21 and circ2010111 I01Rik) confirmed the accuracy of RNA-seq.Conclusions SAH alters the expression of circRNA in mouse cortex and the differentially expressed circRNA may be involved in regulation of EBI following SAH,promising a potential therapeutic target for the diagnosis,treatment and prognosis of SAH.

Predicative value of thrombelastogram in aSAH with delayed cerebral ischemia / 中国神经精神疾病杂志

Objective To investigate the clinical value of thrombelastogram (TEG) in prediction for the cause of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods In this study, there were 30 patients with DCI (group DCI) and 45 patients without DCI (group No-DCI). TEG was performed in all the patients at post-bleeding day 1, 5, 10 and 15 after aSAH(PBDn, n=1,5,10,15). The changes of reaction time (R value), coagulation time (K value),coagulation angle (α value),maximum thrombus consistency (MA value) and coagulation index (CI value) were examined at different time points after aSAH. Results Thirty of 75 aSAH patients developed DCI and the incidence of DCI was 40 percent. According to linear mixed model, both MA value and CI value were significantly statistical different at different time points within each group (P<0.05,for all) as well as between No-DCI group and DCI group.MA value and CI were significantly statistical different at same time point (P<0.05,for all). The results of logistic regression analysis showed that modified Fisher levelⅢ-Ⅳ,△MA5-1(OR=1.124,P=0.024,95% CI=1.015~1.244), PBD5 MA>70(OR=5.605,P=0.011,95% CI=1.464~21.457)were the independent risk factors of DCI.By using ROC curve to define a threshold for prediction of the occurrence of DCI,the rate of DCI was significantly increased when △MA5-1>3.05.Conclusion aSAH Patients, especially those with DCI have severe hypercoagulation. The MA value in PBD5 has an important predictive value for DCI.

Effect of olipoprotein E mimetic peptide on neuronal apoptosis and autophagy after traumatic brain injury / 中华神经医学杂志

Objective To investigate the effect ofolipoprotein E (ApoE) mimetic peptide on neural apoptosis and autophagy and their mechanisms in mice after traumatic brain injury (TBI).Methods A total of 40 health adult male C57BL/6J mice were randomly divided into sham-operated group,TBI+normal saline (NS) group,TBI+COG1410 (1 mg) group and TBI+COG1410 (2 mg) group (n=10).The TBI models of moderate mice were constructed by controlled cortex impact (CCI) devices in the later three groups and mice in the sham-operated group were performed bone window operning only.Thirty min after model making,COG1410 treatment was given by intravenous injection of COGl410 via the tail vein at a dose of 1 mg/kg.d or 2 mg/kg.d.Mice in sham-operated group and TBI+NS group were injected with equal sterile NS instead.Neurological functions were tested 3 d after TBI by rolling-bar test and modified neurological severity scale (mNSS).Neural apoptosis was analyzed by TUNEL and autophagy protein LC3 expression in the neurons of cortex around the lesion focus was detected by immunofluorescence.Western blotting was employed to detect the expressions of apoptosis-related proteins (Bax,Bcl-2 and Caspase-3) and autophagy proteins (Beclin-1,LC3-Ⅰ and LC3-Ⅱ),and changes of Akt,mTOR,phosphorylated-(p-) Akt,p-mTOR levels.Results As compared with those in the sham-operated group,significantly shortened rotarod latency,significantly increased mNSS scores,significantly increased Bax and Caspase-3 protein expressions,significantly decreased Bcl-2,significantly increased Beclin-1 and LC3-Ⅱ protein expressions and number of TUNEL postive neurons,and statistically increased p-Akt and p-mTOR levels in the TBI+NS group were noted (P＜0.05).As compared with those in the TBI+NS group,significantly increased rotarod latency,significantly decreased mNSS scores,significantly decreased Bax and Caspase-3 protein expressions,significantly increased Bcl-2,significantly decreased Beclin-1 and LC3-Ⅱ protein expressions and number of TUNEL postive neurons,and statistically increased p-Akt and p-mTOR levels in the TBI+COG1410 (1 mg) group and TBI+COG 1410 (2 mg) group were noted (P＜0.05).As compared with those in the TBI+COG 1410 (1 mg) group,significantly increased rotarod latency,significantly decreased mNSS scores,significantly decreased Bax and Caspase-3 protein expressions,significantly increased Bcl-2 expression,significantly decreased Beclin-1 and LC3-Ⅱ protein expressions and number of TUNEL postive neurons,and statistically increased p-Akt and p-mTOR levels in the TBI+COG1410 (2 mg) group were noted (P＜0.05).Conclusion ApoE peptide is effective in reducing the excessive neuronal apoptosis and neurological dysfunctions caused by excessive neuronal autophagy after TBI,which is associated with the modulation of Akt/mTOR related pathway.

Downregulation of thioredoxin-interacting protein attenuates early brain injury after subarachnoid hem- orrhage of rats / 中国神经精神疾病杂志

Objective To explore the possible mechanism by which thioredoxin-interacting protein (TXNIP) par?ticipated in early brain injury (EBI) of subarachnoid hemorrhage (SAH) via examination of the expression of TXNIP and its downstream apoptotic factors before and after intervention. Methods Subarachnoid Hemorrhage (SAH) was performed by endovascular perforation. Total 97 adult male SD rats were randomly divided into 6 groups:sham-operation (17), SAH (32), control siRNA (12), TXNIP siRNA (12), resveratrol control (12) and resveratrol injection (12). Western blot was used to examine the expression of TXNIP, p-ASK-1, Caspase-3 before and after intervention. Laser scanning confocal microscopy (LSCM) was used to detect the expression of TXNIP in neurons. The co-localization of TXNIP with apoptotic cells was examined by using fluorescent TUNEL. Mortality, behavior score and cerebral edema were also evaluated. Re?sults Mortality, behavior scores and brain edema were improved after TXNIP siRNA and resveratrol injection(P<0.05). LSCM showed that TXNIP was widely expressed in brain and mainly located in cytoplasm of neurons in SAH rats. Fluo?rescent TUNEL revealed the co-localization of TXNIP with apoptotic cells. The expression level of TXNIP was signifi?cantly higher in SAH group than in sham operation (P<0.05, n=3). The expression level of TXNIP gradually increased at 12h and still remained at high level at 72h (P<0.05). This increase was simultaneously accompanied by the increase in downstream apoptosis factors, p-ASK-1 and Caspase-3. Inhibition of TXNIP by siRNA or resveratrol significantly re?duced the expression of TXNIP, p-ASK-1 and Caspase-3 (P<0.05, n=3). Conclusion TXNIP gradually increases in ear?ly period after SAH and aggravates brain damage through activation of ASK-1 apoptosis signaling pathway, whereas inhi?bition of TXNIP may attenuate EBI through reduction of p-ASK-1 and Caspase-3 after SAH.

The accuracy of Computed Tomography Angiography (CTA) in diagnosis of multiple intracranial aneurysms / 中国神经精神疾病杂志

Objective The purpose of this study is to explore the clinical value of CT angiography( CTA) in the diagnosis of multiple intracranial aneurysms.Methods The data of CTA and DSA from 74 patients with multiple intracra-nial aneurysms from July 2011 to March 2015 were reviewed retrospectively.Results One hundred seventy-seven aneu-rysms were detected by DSA, and 175 aneurysms were detected by CTA.Among the aneurysms identified by CTA, 4 aneu-rysms were false positive and the correct detection rate of CTA was 96.6%.One hundred sixty-five aneurysms identified by CTA were confirmed by DSA and the correct diagnostic rate of CTA was 96.5%.CTA failed to detect 6 aneurysms and mis-diagnosed 10 aneurysms.Conclusions The correct detection rate and diagnostic rate of CT angiography ( CTA) in multiple intracranial aneurysms is relatively high.But previous surgery, spasm of the vessels, the size and number of aneurysms, radiologists'experience can influence the accuracy of ( CTA) in the diagnosis of multiple intracranial aneurysms, indicating that we should combine CTA with DSA to avoid the misdiagnosis and missed diagnosis.

Implementation of personalized medicine concept in the clinical teaching of glioma surgery / 中华医学教育探索杂志

Objective To explore the value of applying personalized medicine in the clinical teach-ing of glioma surgery. Methods Totally 80 7-year program undergraduates were divided into experimental class and control class randomly, with 40 cases in each group. The experimental class received personalized medical teaching through introducing idea and method of personalized medicine. The control class received conventional teaching. The effect of teaching was evaluated by questionnaire and examination. The data were analyzed through Chi-square and t-test test. Result Questionnaire survey of satisfaction showed that 37 students of experimental class (92.5%) were interested in the new course. Questionnaire survey of teaching effect showed that in experimental class 36 students (90%) felt it could increase learning interest, 37 students (92%) believed it improved glioma diagnosis and treatment, 34 students (85%) felt their medical view ex-panded, 38 students had consolidated clinical thinking, and 32 students (80%) improved negotiation with patients. All issues were significantly better than control class (P<0.05). Meanwhile, statistical difference was found in average score between experiment class and control class [(88.71 ±6.54) vs. (76.49 ±7.32)] (P=0.000). Conclusion The introduction of personalized medicine concept helps medical students to make personalized diagnosis and treatment plan for glioma patients, and is conducive to the cultivation of their clinical thinking ability and evidence based medicine concept, which is worthy of promotion.

Primary Schwann cell growth on electrospun polymethyl methacrylate nanofiber scaffolds / 中华创伤杂志

Objective To evaluate the value of electrospun polymethyl methacrylate (PMMA) nanofibers with different topological structures as scaffolds for growth of Schwann cells (SCs).Methods Electrospun PMMA nanofibers with random or aligned topological structures were fabricated and measured with biocompatibility.Lentivirus-transfected green fluorescent protein was used as the reporting gene to monitor form and growth manner of SCs on different substrates and dependency of cell body and process with fiber structure,with PMMA thin films served as the control.Results Electrospun PMMA nanofibers revealed good biocompatibility and could exert contact guidance to the growth of SCs.Topological structures of the electrospun nanofibers influenced cell morphology.SCs were aligned with the orientation of substrate fibers and form longer cell process when growing on aligned nanofibers (P ＜0.01).Primary SCs preferred to follow the cue of aligned nanofibers compared to random fibers.Conclusion Aligned electrospun PMMA nanofibers have the potentiality as transplantable scaffolds for loading SCs after neural injury.

Effect of cog1410 on brain edema around lesion foci of mice with traumatic brain injury / 中华创伤杂志

Objective To investigate the effect of cogl410 on brain edema around lesion foci after traumatic brain edema (TBI) in mice and possible mechanism.Methods APOE-knockout TBI mice (n =130) were divided into cog1410 group and saline group according to the random number table,with 65 mice per group.Several time points (0,1,3,5,and 7 days) after TBI,13 mice were sacrificed in each group.TBI was induced with controlled cortex injury to the mice.A single injection of cog1410 solution or saline was administered via the caudal vein in 30 minutes after TBI.Levels of aquaporin-4 (AQP-4) around the lesion tissues were measured using the Western blot and q-PCR methods.Brain water content was determined by the dry-wet weight method.Results Brain water content in cog1410 group and saline group increased after TBI,reached the peak at day 3 [(81.184 ±0.009)％ vs (84.184 ± 0.014) ％] and normalized at day 7 [(76.018 ± 0.003) ％ vs (77.790 ± 0.012) ％] (P ＜ 0.05).There were almost no changes in AQP-4 mRNA expression in saline group after TBI.Whereas in cog1410 group,AQP-4 mRNA was greatly down-regulated at day 3 (0.278 ±0.014),increased greatly at days 5 and 7 after TBI (1.744 ± 0.014,1.782 ± 0.003) (P ＜ 0.05).Level of AQP-4 protein in saline group was increased at day 1 (0.491 ±0.060),reached the peak (0.605 ±0.099),and gradually returned to the preinjury level at days 5 and 7 (0.434 ± 0.042,0.358 ± 0.034).By contrast,level of AQP-4 protein in cog1410 group revealed no notable changes at day 1,slight increase at day 3,significant increase at day5 (1.079±0.090),and apeak at day7 (1.247±0.210) (P＜0.05).Conclusion cog1410 can significantly alleviate brain edema around the lesion foci of mice with TBI,as may be achieved by altering the mRNA and protein levels of AQP-4.

Impact of topographic features of electrospun polymethylmethacrylate nanofibers on growth pattern of rat primary astrocytes / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the impact of the topographic features of electrospun polymethylmethacrylate (PMMA) nanofibers on growth pattern of primary rat astrocytes.</p><p><b>METHODS</b>Rat astrocytes were cultured on fabricated random and aligned electrospun nanofibers. Using PMMA film as the control, the cells were transfected with a lentivirus harboring GFP gene to reveal the cell growth pattern on different substrates.</p><p><b>RESULTS</b>oth random and aligned electrospun PMMA nanofibers could support the growth of rat astrocytes, but the topographic features of the fibers significantly affected their growth pattern. On aligned nanofibers, astrocytes extended long cell processes along the direction of the substrate fibers, and on random fibers the astrocytes formed shorter processes. On merged images of GFP expressions and substrate fibers, the cell processes of the astrocytes were shown to adhere to and elongate along the fibers both on random and aligned nanofibers.</p><p><b>CONCLUSION</b>The topographic features of PMMA nanofibers can significantly influence the growth pattern of primary rat astrocytes. Aligned electrospun nanofibers has the potential to serve as scaffold material for reducing glia scar formation after spinal cord injury.</p>

Effect of apolipoprotein E genetic polymorphism in repair of blood brain barrier breakdown following traumatic brain injury / 中华创伤杂志

Objective To investigate the effect and underlying mechanism of apolipoprotein E (APOE) genetic polymorphism in treating blood brain barrier (BBB) breakdown after traumatic brain injury (TBI).Methods Human APOE knock-in mice (ε3,ε4),APOE knockout mice,and APOE wild-type mice with each numbering 80 were respectively divided into TBI group (n =50),sham-operation group (n =15) and normal control group (n =15) according to the random number table.TBI group was subdivided at 1 day (n=15),3 days (n=15),and7 days (n=20).TBI was induced with a pneumatically operated injury device.BBB permeability to large or small molecules was evaluated by measuring Evans blue (EB) and fluorescein sodium (NaFI) extravasation into the damage area at 1,3,and 7 days postinjury.Brain water content was determined using the dry-wet method.Western blotting and qRT-PCR for tight junction-associated proteins Occludin and Claudin-5 were performed at 7 days postinjury.Results With respect to normal control group,BBB permeability to EB and NaFI was significantly higher in ε4 and APOE knockout mice than in ε3 and APOE wild-type mice.There appeared significant increase in BBB permeability to EB and NaFI in TBI group,with insignificant differences among rats of each genotype at 1 and 3 days postinjury (P ＞ 0.05).Whereas at 7 days postinjury,BBB permeability to EB in APOE wild-type and e3 mice returned to the normal level (P ＞ 0.05),but it re mained at a high level in APOE knockout and ε4 mice (P ＜ 0.01).Meanwhile,BBB permeability toNaFI was significantly higher in ε4 and APOE knockout mice than in ε3 and APOE wild-type mice (P ＜ 0.01).Brain water content was equivalent among rats of each genotype at 1,3 and 7 days postinjury (P ＞0.05).Western blotting and qRT-PCR demonstrated Occludin and Claudin-5 in ε4 and APOE knockout mice were significantly lower than those in ε3 and APOE wide-type mice (P ＜ 0.05).Conclusion APOE plays an important role in restoration of BBB function after TBI,but ε4 may impede the recovery of BBB breakdown after TBI through its effect on tight junction.

Effect of apolipoprotein E polymorphisms on expression of p38MAPK in the early period of astrocytes injury / 中华创伤杂志

Objective To investigate the correlation between apolipoprotein E (APOE) polymorphisms and expression of p38MAPK of injured astrocytes in the early stage.Methods Scratch injury to astrocytes of three different alleles of APOE (ε2,ε3,andε4) was induced.RT-PCR and Western-blot were applied to detect dynamic changes of intracellular p38MAPK before injury and at 12,24,48,and 72 hours postinjury.Results Expression of p38MAPK in APOEε2,ε3,andε4 astrocytes increased gradually over time,whereas before and 12-hour after injury,the difference was insignificant in pair comparison (P ＞ 0.05).p38MAPK in APOEε2,ε3,andε4 astrocytes revealed progressive up-regulation at 24,48,and 72 hours postinjury,but the expression in APOEε4 astrocytes was the highest (P ＜ 0.05).Conclusion In the early period of injury,highly expressed p38MAPK in APOEε4 astrocytes indicates a more active p38MAPK-induced inflammatory response in APOEε4 carriers which may contribute to acute exacerbation and poor outcome.

Correlations between AT1R gene polymorphism with AT1R mRNA and protein expression difference in brain tissue after hypertensive cerebral hemorrhage / 重庆医学

Objective To investigate the correlation of angiotensin Ⅱ type 1 receptor (AT1R) gene polymorphism with AT1R expression levels and brain edema after hypertensive intracerebral hemorrhage .Methods 45 operative patients with hypertensive intracerebral hemorrhage in the Affiliated Yongchuan Hospital of Chongqing Medical Univercity from December 2011 to August 2012 were collected as the experimental group and 45 operative patients with refractory epilepsy weres selected as the control group .The venous blood in the two groups were collected for detecting the AT 1R gene polymorphism ;The brain tissue was taken from lesions in operation ,then AT1R mRNA concentration was determined by RT-PCR and the AT1R protein level was determined by Western blot ;Head CT was performed on postoperative 1 ,3 ,5 d;the degree of cerebral edema was reflected by CT value . Results The levels of two kinds of genotype AT1R mRNA in the experimental group had no statistically significant difference(P>0 .05);the operative area CT value of AC genotype was significantly lower than that of AA genotype with statistical difference (P<0 .05);the ATIRmRNA of various genotypes ,protein level and cerebral edema in the control group had no statistical differences . Conclusion The AT 1R gene polymorphism has no obvious correlation with the concentration expression of AT 1R mRNA in the brain tis-sue;there is correlation between AT 1R protein level and AT 1R protein level and the cerebral edema degree in the brain tissue .