Objective To observe if endothelial progenitor cells (EPCs) and bone marrow mesenchymal stem cells (BMSCs) could home to the injured region and study the effect of BMSCs-derived EPCs on traumatic brain injury (TBI) in rats.Methods BMSCs were isolated from 3-month-old SD male rats weighing 150 g,and induced to EPCs.EPCs were identified by surface markers CD133,CD34 and FLK-1.A total of 120 female adult SD rats were divided into 3 groups (n =40 each) according to the random probability table method:EPCs group,BMSCs group and 3T3 cells group.The model of moderate to severe TBI was induced by the fluid percussion device.All the cells (i.e.EPCs,BMSCs and 3T3 cells) were injected with BrdU before transplantation to the tail vein of rats.On days 2,7,14 and 28 after transplantation,rat neurological function was evaluated using the modified neurological severity score (mNSS),and injured brain tissue was harvested to detect CD34 and brain-derived neurotrophic factor (BDNF) positive cell density using the immunohistochemistry method.Sry-positive cells were evaluated using the fluorescence in situ hybridization (FISH).Results The positive rate of CD133,CD34 and Flk-1 was 52％,33％ and 38％,indicating BMSCs differentiation towards an EPCs phenotype.On days 7,14 and 28 after transplantation,the mNSS in EPCs group [(10.2 ± 1.5),(8.7 ± 1.0) and (4.9 ± 1.0) points] and in BMSCs group [(10.8 ± 1.7),(10.1 ± 1.7),and (7.2 ± 1.3) points] were lower than that in 3T3 cells group [(12.4 ± 1.5),(1 1.7 ± 1.8),(10.3 ± 1.5) points] (P ＜ 0.05).On 14 and 28 days after transplantation,BrdU-positive CD34 and BDNF in EPCs group were significantly more than those in BMSCs group (P ＜ 0.05).Instead,there were no positive cells in 3T3 cells group.The method of Sry probe to trace the transplanted cells could detect more positive cells compared to the BrdU labeling method.Conclusion Both BMSCs and EPCs can home to the injured region,but EPCs have much better therapeutic effect.

Objective To explore the changing rule and clinical significance of the abnormal cortical secretion resulted from traumatic brain injury (TBI). Methods The serums from 55 TBI patients and 13 normal persons were collected to measure the level of secreting total cortisol (Cor) , adrenocorticotropin (ACTH) and corticosteroid-binding-globulin (CBG) by using radioimmunoactive assay and chemiluminescent immunometric assay. In the meantime, the free cortisol (FC) and free cortisol index (CI) were calculated by using Coolen formula. Results CBG maintained stable, while Cor and other hormones were increased significantly with the severity of TBI. Surgical operation could release the stress partially without disturbing the secretion of hormone. The more quickly the serum hormone decreased, the better prognosis the patients would have. The lower level of Cot could result in poorer prognosis. Conclusions TBI can result in a higher level of Cor as well as other hormones in the serum. The prognosis is poor in patients with a persistent high or low level of Cor. It should be cautious to supply large volume of cortisol at the early phase of TBI.

Objective To investigate the protective effect of hypoxia-inducible factor-1α(HIF-1 α) on the neurovascular unit in rats with traumatic brain injury (TBI).Methods The fluid percussion model was applied to induce TBI in rats.A total of 600 rats were divided into sham operation group,TBI group,TBI + HIF-1 α silence group and TBI + control virus group according to the random number table,with 150 rats in each.Virus-mediated HIF-1 α silence gene and control virus were delivered 24 h before the fluid percussion injury.After 3,7 and 14 d,brain injury area and morphological changes in injured region were detected by HE staining,expressions of vascular endothelial cell markers (vWF) and HIF-1 α were detected by Western blot method,and expressions of vascular endothelial growth factor (VEGF),matrix metalloproteinase-9 (MMP-9),tumor necrosis factor-α (TNF-α),interleukin 6 (IL-6) and nuclear factor-κB (NF-κB) in peripheral blood and brain tissue were detected by ELISA method.Rat neural function was dynamically assessed using the modified neurological severity score (mNSS).Results (1) Brain injury area and edema area in TBI + HIF-1 α silence group were higher than those in TBI group at all time points (P ＜ 0.05).(2) Compared with sham operation group and TBI + control virus group,expression of HIF-1α in TBI group gradually increased and remained high at 7 and 14 d postinjury (P ＜ 0.05).Compared with TBI group,expression of vWF in TBI + HIF-1αsilence group decreased at all time points (P ＜ 0.05) and inhibited angiogenesis.(3) TBI + HIF-lα silence group versus TBI group showed remarkably decreased VEGF at all time points,increased expressions of TNF-α,IL-6 and NF-κB at all time point,and increased expression of MMP-9 at 7 and 14 d postinjury (all P ＜0.05).(4) TBI + HIF-1α silence group versus TBI group showed significant difference in mNSS at 7 and 14 d postinjury (all P ＜ 0.05).Conclusions After TBI,high expression of HIF-1αcan facilitate vascular formation and inhibit inflammatory reaction related factor expression,inducing the mitigation of brain edema and brain injury.Therefore,promoting HIF-1α expression may become a new means to improvement of neurovascular function after TBI.

Traumatic brain injury is always associated with hemorrhage and coagulopathy, leading the occurrence of anemia, platelet function inactivation, platelet and coagulation factor consumptive reduction. Theoretically, transfusion therapy should be given to supplement the missing component in an appropriate range. However, whether the transfusion therapy can improve the prognosis of patients with traumatic brain injury, and the indications of transfusion, have been the focus of academic debate for a long time. This article reviews the latest progress of transfusion therapy in traumatic brain injury, and provides reference for better guidance of transfusion in clinical treatment.

Objective: To compare the inhibitory effect of carmustine(BCNU) and bleomycin on craniopharyngiomas in vitro. Methods: Cells were successfully cultured in vitro from the fresh specimens, then the culture medium with bleomycin or BCNU at different concentration was added. The tumor inhibitory curve-line was drawn based on the cell number at different time points. After cultured for 144 h, ATP-luminescence assay was applied to test the antitumor effect. Results: The cell number decreased rapidly when the medium was added. The decreasing speed was faster in BCNU medium than that in bleomycin medium at the same concentration. The bleomycin medium showed no significant inhibitory effect except for the one at 1.00 g/L. However, regardless of the concentration, BCNU medium inhibited the cells effectively. Conclusion: BCNU has stronger inhibitory effect on craniopharyngiomas cells than bleomycin, it can be used to treat this tumor

Objective To study the effect of simvastatin (SIM) on the expression of neuron specific enoalse (NSE) in rat brain and serum after traumatic brain injury (TBI), and therapeutic effects of SIM on TBI thereof. Methods A total of 90 Sprague-Dwalye (SD) rats aged 8 weeks were randomly divided into sham TBI group, control group and treatment group (n=30). The TBI model was established in control group and treatment group by using Feeney method. Rats in treatment group were fed SIM 10 mg/kg in the evening pre-injury and in every evening post-injury while those in control group were fed the same dose of starch at the same time. Blood samples (3 mL) were collected from carotid atrery in three groups, then rats were sacrificed and brains were collected at different time points (3 h, 12 h, 24 h, 3 d, 7 d and 14 d post-injury). The serum ex-pressions of NSE were detected by ELISA method. The NSE expressions in hippocampal area CA3 were detected with immu-nohistochemistry. Results (1) In control group, the serum NSE level was significantly increased at 3 h after injury, reached the peak at 3 d, and was still higher than that of sham injury group at 14 d. In treatment group, the serum NSE level was in-creased 3 h after injury, reached the peak at 24 h, decreased after 3 d, and was near the sham injury group at 14 d after inju-ry, but was significantly lower than that of control group. (2) Immunohistochemical detection showed that the NSE optical density values in hippocampal area CA3 area were decreased at 3 h after injury in control group. The optical density values reached the lowest level between 3 d to 7 d and were still significantly lower than those of sham injury group at 14 d. In treat-ment group the optical density value was decreased at 3 h after injury, reached the lowest level between 12 h to 24 h and re-bounded significantly at 7 d, then at 14 d up to the level of sham injury group. Conclusion SIM can promote the decrease of serum NSE level in TBI rats and increase the NSE expression of hippocampal neurons of injured side, showing protective effects on neuronal damage after traumatic brain injury.

Fingolimod (FTY720) as a new immunosuppressive agent,is the prodrug of an sphingosine-1-phosphate receptor agonist.It is a potent immunosuppressant which has been approved by the US Food and Drug Administration to treat relapsing-remitting multiple sclerosis,and shows its unique and novel mechanism of action.Unlike the traditional immunosuppressive agents,fingolimod exerts immunosuppressive and immunoregulatory functions mainly through interaction with shhingosine-l-phosphate receptors on the cell surface without affecting activation and proliferation of lymphocytes.In addition,FTY720 has been shown to inhibit a variety of cancer related signal transduction pathways.It also presented significant anticancer effects in the in vivo and in vitro experiments.And in the treatment of glioblastoma multiforme (GBM) experiment,FTY720 displayed excellent activity as well had a synergistic effect in addition to temozolomid,the current standard chemotherapeutic agent to treat malignant gliomas.This article reviewed the advances in study on the anti-GBM effect and mechanism of FTY720.

Exosomes are homogeneous membrance-derived microvesicles shed by cells,their sizes ranged from 40 to 100 nm.As for microparticles,they are small heterogeneous vesicles at diameters of 100 to 1000 nm shed by cells.Both of them exist in a wide range of body fluids,including peripheral blood,urine,saliva,ascites,amniotic fluid and cerebrospinal fluid,with various kinds of biomolecules like proteins and RNAs.Exosomes and microparticles play important roles in cell-to-cell information transmissions and substance exchanges,contributing to both physiological and pathological processes.Exosomes,functioning as the carders of material transportation,serve as targeted therapy in disease treatments.Microparticle,a new type biomarker,plays an important role in diagnosing the early-stage of diseases and predicting the prognoses.The central nervous system diseases are lacked of early-stage diagnoses and effective treatments because of the complexity and unpredictability.This review is to focus on the specific comparisons between exosomes and microparticles as well as their central nervous system functions and mechanisms,and also to explore the new treatments of the central nervous system diseases.

OBJECTIVETo study the gene expression profiles of oligodendrogliomas with gene cDNA array.

METHODS(32)P tagged cDNA probes converted from the total RNA, which had been extracted from 2 fresh samples of oligodendroglioma and 1 of normal brain tissue, were hybridized with the Atlas array. After washing the membranes, the autoradiography was performed and the autoradiograms were analyzed through the special software.

RESULTSAs compared to the normal brain tissue, there were 63 co-upregulated genes and 4 co-downregulated genes in these 2 tumor samples. However, a significant quantitative difference existed between them. The expression trend of some genes differed from the known information.

CONCLUSIONcDNA array is effective for studying the gene expression profiles of oligodendrogliomas and provides new information for the further research on their molecular mechanisms.

Brain Neoplasms ; genetics ; pathology ; Gene Expression ; Gene Expression Profiling ; Humans ; Oligodendroglioma ; genetics ; pathology ; Oligonucleotide Array Sequence Analysis ; methods ; Reverse Transcriptase Polymerase Chain Reaction