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Mesoporous silica nanoparticles (MSNs) are attracting increasing interest for potential biomedical applications. With tailored mesoporous structure, huge surface area and pore volume, selective surface functionality, as well as morphology control, MSNs exhibit high loading capacity for therapeutic agents and controlled release properties if modified with stimuli-responsive groups, polymers or proteins. In this review article, the applications of MSNs in pharmaceutics to improve drug bioavailability, reduce drug toxicity, and deliver with cellular targetability are summarized. Particularly, the exciting progress in the development of MSNs-based effective delivery systems for poorly soluble drugs, anticancer agents, and therapeutic genes are highlighted.
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Objective@#To express and purify outer membrane protein FomA of Fusobacterium nucleatum (Fn) through gene recombination technique with Escherichia coli (Ec) expression system, and to detect the immunogenicity and the immune effects of the recombinant protein on gingival tissues.@*Methods@#The gene recombination technique and Ec expression system were used to express and purified the FomA protein. Totally 20 C57 mice were immuned with the protein or the phosphate buffer solution (PBS) buffer by subcutaneous injection (each 10 mice), and the specific FomA antibody was detection in mice serum. The immunogenicity of FomA protein was assessed by comparing the differences between groups. Furthermore, the model of mice gum abscess was constructed with Fn or Fn and Porphyromonas gingivalis (Pg) mixed suspension used the above mice. The score of the gingival abscess was recorded and the interleukin (IL)-1β in gum tissue and mice serum was determined by enzyme-linked immunosorbent assay method, and the differences of the indexes between groups were compared to evaluate the effect of the FomA protein immunization.@*Results@#Totally 1.0-1.5 g FomA protein were successfully obtained and the protein purity was over 90%. The FomA specific antibody was detected in the serum of mice by subcutaneous injection of the protein, and the antibody titer reached the highest level in 2 weeks after secondary immunization. The model of submaxillary gingival abscess was successfully constructed. In the Fn model, the score of the FomA protein immune group was (1.82±0.35), and the PBS control group was (2.62±0.71), with statistically significant difference between the two groups (P=0.049). In the Fn+Pg mixture model, the score of gingival abscess in the FomA immune group (2.31±0.55) was lower than that in PBS group (3.63±0.45), and the difference was statistically significant (P=0.003). Both in Fn and Fn+Pg injection group, the concentration of IL-1β in the serum of FomA immune mice and gingival tissues was lower than that of PBS control mice (P<0.001).@*Conclusions@#The recombinant FomA protein can be acquired by Ec expression system, and it can produce a certain level antibodies in the mice serum. The way of mice subcutaneously injected with the recombinant FomA protein can reduce the severity of periodontal infections caused by Fn and Pg.
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Objective To evaluate the clinical effect of dextromethorphan and its effect on daily living of patients with poststroke pseudobulbar affect. Methods Sixty patients with poststroke pseudobulbar affect admitted in our hospital from May 2013 to October 2016 were enrolled. Then they were randomly divided into the control group and the treatment group,with 30 patients in each group.Patients in the control group were treated with fluox-etine therapy and patients in the treatment group were treated with dextromethorphan therapy.The center for neuro-logic study lability scale(CNS-LS)and activity of daily living(Barthel index,BI)before and 30 days after the treat-ments in the two groups had been accessed. Results Thirty days after the treatment,CNS-LS of the treatment group had obvious improvement compared with that before treatment(P < 0.01),but CNS-LS of the control group had no obvious improvement compared with that before treatment(P > 0.05). And significant improvement has been found 30 days after the treatment between the two groups(P<0.01).Furthermore,significant difference was found on BI between these two groups(P<0.05).Conclusions Dextromethorphan is effective in treatment of pa-tients with poststroke pseudobulbar affect and it can improve the activity of daily living of these patients.
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Objective To explore effect of increasing cerebrospinal fluid (CSF) leptin level by administration from the foramen magnum to the cerebellum medulla oblongata pool in osteoporosis in rabbit model established by ovariectomy (OVX) and methylprednisolones.Methods According to certain inclusion and exclusion criteria,30 adult rabbits which were healthy 5-month-old female New Zealand white rabbits with the same batch and weight were divided into 5 groups (n=6) with random number table,including control group,normal saline group,Low dose group,middle dose group and high dose group.The animal model of osteoporosis (OP) was established 8 weeks after ovariectomy (bilateral ovarian resection) and intramuscular injection of methylprednisolone daily for 8 consecutive weeks in all groups.The control group were only simulated puncture and didn't inject any drugs or normal saline,the normal saline group were intracerebroventricular (ICV) injection with NS and Low,Middle and High dose group injected with low,middle and high dose of leptin respectively at 0,3,7 days after OVX.Before (0 week) and 4,8 weeks after the operation,the measure of dual energy X-ray absorptiometry was done on all the rabbits femur and bone mineral density (BMD) was delivered.Before (0 week) and 4,8 weeks after the first administration,leptin in cerebrospinal fluid (CSF) and serum growth hormone (GH),insulin growth factor 1 (IGF-1) and osteocalcin (OT/BGP) were tested with Enzyme linked immunosorbent assay and serum calcium,phosphorus and alkaline phosphatase (ALP) with automatic biochemical analyzer (ACA).The rabbits were sacrificed and the thalamus and femoral neck were harvested to test the expression of leptin receptor (LEPR) in thalamus and bone morphogenetic protein-2 (BMP-2) and type Ⅰ collagen (Col Ⅰ) at 8 weeks after the first administration.Results Compared with the control group and NS group,the cerebrospinal fluid (CSF) leptin concentration of leptin administration groups kept in a higher level significantly at 4 and 8 weeks after leptin administration,it was positively correlated with the concentration of administration.After administration 4 and 8 weeks,the bone mineral density (BMD) of leptin administration groups were not significantly lower than that of non-administration groups,and the high dose group was unchanged.The serum osteocalcin/bone glad protein (OT/BGP) concentration of leptin administration groups decreased more significantly compared with the non-administration groups at 4 weeks after leptin administration;and it rebounded more significantly than the non-administration groups and low dose group rebounded more significantly than other non-administration groups at 8 weeks.The concentration of serum growth hormone (GH) of 5 groups showed a downward trend at 4 and 8 weeks,the serum GH concentration of leptin administration groups decreased more significantly than the non-administration groups.The concentration of serum insulin-like growth IGF-1 of 5 groups were decreased significantly at 4 weeks,and the serum IGF-1 concentration of control and low dose groups were significantly higher than other 3 groups at 8weeks.Compared with the non-administration groups,the concentration of serum Calcium of leptin administration groups were increased more obvious,and it was positively correlated with the concentration of administration.Serum phosphorus of 5 groups were decreased at 4 weeks and elevated at 8 weeks;there was no difference among the groups.Serum ALP showed a continuous downward trend,and the middle dose group decreased significantly compared with other groups at 4 and 8 weeks.RTPCR results showed that the BMP-2 and Col Ⅰ mRNA expression increased and positively correlated with leptin administration concentration at 8weeks.Conclusion The increase of cerebrospinal fluid leptin level can promote the bone metabolism,reduce bone loss and precaution the occurrence of osteoporosis in rabbit model caused by OVX and methylprednisolone,and it was positively correlated with the concentration of administration.That provides a new method for the prevention and treatment of osteoporosis in rabbit model.
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Objective:To explore whether Tuftsin can attenuates symptoms in experimental autoimmune encephalomyelitis mouses.Methods:C57BL/6 mice were immunized with MOG35-55 peptides,and evaluated for clinical neurological score every day .10 mice of the EAE were injected with Tuftsin subcutaneously .The spinal cord were stained by the methods of Haematoxylin Eosinstain , Luxol Fast Blue stain.The mRNA expression of IL-10 and TNF-αfrom brian tissue were detected at the 28 days by RT-PC method.Results:The controlled mice had no symptoms of disease and HE ,LFB were normal.Comparison EAE group with Tuftsin group of HE,LFB,EAE group were server than Tuftsin group.The expression of IL-10 in Tuftsin group was higher than EAE group.The expression of TNF-αin Tuftsin group was lower than EAE group .Conclusion: Tuftsin can attenuates symptoms in experimental autoimmune encephalomyelitis mouses .
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Objective To investigate effect of taurine on respiration chain enzyme activity of mitochondria 24 hours after severe traumatic brain injury (TBI) in rats.Methods Fifty-six SD rats were divided into sham group,TBI group,taurine treatment group,and taurine prevention group according to the random number table,with 14 rats per group.Fluid percussion brain injury models were used.Via the caudal vein,normal saline was administered to animals in sham and traumatic brain injury groups immediately after injury,while taurine (200 mg/kg)was administered to animals in taurine treatment group after injury and in taurine prevention group 4 days before injury.Brains were harvested 24 hours postinjury for assays of HE staining and electron microscopy.Mitochondrial respiratory chain complex Ⅰ-Ⅴ activities were detected.Results TBI group presented swelling neurocytes,cell loss,karyopyknosis,shortened even vanished process,and inflammation cell infiltration at the edge of necrosis in HE staining.By contrast,morphological improvement was significant in taurine treatment group but only some neurons were intact in taurine prevention group.Swelling mitochondria and broken or vanished mitochondrial crests were seen in TBI group under the electron microscope.However,normal or minor swelling mitochondria was seen in taurine treatment group and cytoplasm slightly porous and absence of mitochondrial crests were seen in taurine prevention group.Activities of complex Ⅰ,Ⅱ and Ⅴ were significant lower in TBI group (32.52±2.41,4.68 ±0.15,2.49 ±0.73) compared to those in sham group (34.03 ±0.46,5.04 ±0.29,3.20±0.68) and in taurine treatment group (33.95±0.85,5.12-±0.23,3.53 ±0.48) (P＜0.05).And complex Ⅰ in taurine prevention group was significantly enhanced as well (34.44 ± 0.36,P ＜ 0.05).Conclusion Taurine may protect the brain tissues and mitochondrial structure from impairment in TBI rats by improving mitochondrial enzymes activity and reducing secondary energy loss.
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Hot-melt extrusion was applied to prepare mesoporous silica/ethylcellulose mini-matrix for sustained release, and fenofibrate was used as a model drug, ethylcellulose and xanthan gum were chosen as sustained-release agent and releasing moderator, respectively. This novel matrix obtained the controlled release ability by combining mesoporous silica drug delivery system and hot-melt extrusion technology. And mesoporous silica particle (SBA-15) was chosen as drug carrier to increase the dissolution rate of fenofibrate in this martix. Scanning electron microscope, transmission electron microscope, small angle X-ray powder diffraction and N2 adsorption-desorption were introduced to determine the particle morphology, particle size and pore structure of the synthesized SBA-15. The results showed that SBA-15 had a very high Brunauer-Emmett-Teller specific surface area, a narrow pore size distribution, large pore volume and a ordered two-dimensional hexagonal structure of p6mm symmetry. Differential scanning calorimetry and X-ray powder diffraction results demonstrated that fenofibrate dispersed in an amorphous state inside the pores of the mesoporous silica which contributed to the improvement in the dissolution rate. The drug release of mini-matrices was influenced by ethylcellulose viscosity grades and xanthan gum concentration, which increased with the increasing of xanthan gum concentration and decreasing of ethylcellulose viscosity. Mini-matrix containing 22% xanthan gum exhibited a good sustained release performance, and the drug release behavior followed the first-order kinetics.
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Objective To investigate the effect of taurine transporter in the process of protection of brain edema in rats with severe traumatic head injury. Methods A total of 24 Male Sprague-Dawley rats were randomly divided into 4 groups. Except the control rats (Group Sham), all other three groups were subjected to lateral fluid percussion head injury. The TBI (Traumatic brain injury) models (Group TBI) and surgical control rats (Group Sham) were injected with saline through caudal vein after surgery, while the Taurine prevention and Taurine treatment models (Group Pre Tau and Group Tau) were injected with 120 g/L taurine solution before or after surgeries respectively. Water content in each brain, mRNA and protein expres?sion of aquaporin 4 and taurine transporter in the injured rat brain hemispheres were all evaluated over the time course of the study (7 d) in each group. Results Compared with rats in Group Sham, water content in each brain increase, mRNA tran?scription and protein expression of AQP4 were both up regulated but the mRNA transcription and protein expression of TauT were both down-regulated in rats in TBI group. Compared with rats in TBI group, brain water content, mRNA transcription and protein expression of AQP4 all decrease while mRNA transcription and protein expression of TauT all increase in rats in Pre tau and Tau groups. There is no statistical difference of TauT expression between rats in pre-tau group and Tau group. Conclusion Taurine exert its neuron protection role through draining water content from brain and down regulating expres?sion of AQP4 but rising expression of TauT after TBI.
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Objective To investigate the enhanced osteogenesis during bone fracture healing after intracerebroven-tricular (ICV) leptin injection, using rabbit model with created segmental bone defect in right tibial. Method Segmental critical-sized defects were created at the right tibial bone of skeletally mature New Zealand white rabbits. In experiment group (leptin group), recombinant rabbit leptin was injected into cerebellomedullary cistern through foramen magnum. While in control group, normal saline was injected in the same way. Bone Mineral Density (BMD) was evaluated by qCT at 1st, 3rd, 7th, 14th and the 21st days. At the 21st days, all rabbits were euthanized to collect the right tibia for histomorphology, to ex-amine the BMP-2 expression in the bone callus by Fluorescence in situ hybridization (FISH). Result In the leptin group, body weight declined more obviously than control group then it start to arise at the 14th day;qCT showed significant higher BMD in leptin group than in control group at the 7th day;FISH showed a higher BMP-2 expression in leptin group than in control group. Conclusion Cerebellomedullary leptin injection through foramen magnum could accelerate limb fracture healing in rabbit model with right tibial bone defection.
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Objective To investigate effect of mild hypothermia on changes of somatosensory evoked potential (SEP) and synaptophysin mRNA level after traumatic brain injury (TBI) and determine hypothermia-induced neuroprotection.Methods Forty-five SD rats were allocated into mild hypothermia group,TBI group and sham operation group with 15 rats per group according to the random number table.Left-side fluid percussion impact was performed to induce models of TBI.Rats were exposed to hypothermia environment (32-35℃) for 6 hours in mild hypothermia group after TBI.Rats in sham operation group were treated by only drilling on left side of the head,rather than hitting.To evaluate function outcome,modified neurological severity score (mNSS),SEP and synaptophysin mRNA level were measured at 6 hours,24 hours and 7 days postinjury.Results The mNSS in mild hypothermia group lowered compared with TBI group,especially at 24 hours and 7 days (P ＜ 0.05).SEP in mild hypothermia group was significantly shortened at 6 and 24 hours compared with TBI group (P ＜ 0.05),but SEP revealed no significant difference among the 3 groups at 7 days (P ＞ 0.05).Level of synaptophysin mRNA in mild hypothermia group increased at 6 hours postinjury compared with TBI group [(0.08 ± 0.02) vs (0.12 ±0.04)],with further increase at 7 days postinjury[(0.06 ± 0.01) vs (0.33 ± 0.10)] (P ＜0.05).Conclusion The shortage of nerve conduction time of the injured side and promotion of nerve regeneration suggest the neuroprotective role of mild hypothermia following TBI.
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Objective To investigate the effect of mild hypothermia on neuroprotection and prognosis prediction of rats with traumatic brain injury (TBI) by dynamically monitoring the somatosensory evoked potentials (SEP) and quantitative electroencephalogram (QEEG).Methods Forty healthy adult male SD rats were randomly divided into four groups according to random number table,ie,normal control group (with no intervention),sham operation group (fenestration only,without drilling),TBI group (fluid percussion was used to produce moderate to severe TBI),and mild hypothemia group (ice blanket was used immediately after TBI for continuous physical cooling and rectal temperature was maintained at 32-35℃ and rewarmed to 37℃ 6 hours after the initiation of cooling),with 10 rats per group.Changes of SEP and QEEG in all groups were monitored at 6,24 hours,and 7 days after TBI.Results (1) Compared with TBI group,the latency of SEP waves (P1 and N1) on the injured side in mild hypothemia group began to shorten at 24 hours(P ＜ 0.05) and were close to that in the sham operation group at 7 days.(2) Except for normal control group and sham operation group,QEEG in TBI group showed decrease of α rhythm,increase of reactivity slow waves,and decrease or disappearance of QEEG relative power spectral values at all time points.In mild hypothermia group,the reactivity slow waves were decreased with a small amount of α wave; QEEG relative power spectral values were increased at 24 hours and 7 days (especially at 24 hours),but werc still lower than those in normal control group (P ＜ 0.05).Conclusion Mild hypothermia exerts neuroprotective effect through reducing SEP latency,raising relative power spectral values of QEEG,and improving the nerve conduction and brain electrical activity of the injured side.
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<p><b>BACKGROUND</b>Many researches demonstrate that the secondary brain injury which is caused by autoimmune attack toward brain antigens plays an important role in surgical brain injury (SBI). Although traditional immunosuppression can reduce autoimmune attack, it will lower the body immunity. Immune tolerance, by contrast, not only does not lower the body immunity, but also could lighten autoimmunity. This study used thymus tolerance to develop an immune system that is tolerant to autologous cerebrospinal fluid (CSF) and autologous brain tissue so that autoimmune injury can be suppressed following the disruption of the blood-brain barrier, thereby reducing brain damage.</p><p><b>METHODS</b>Eighty experimental rabbits were divided into five groups by random number table method: 16 in SBI group (group A), 16 in SBI+CSF drainage group (group B), 16 in SBI+CSF drainage+PBS injection group (group C), 16 in SBI+CSF drainage+CSF intrathymic injection group (group D), and 16 in SBI+brain homogenate intrathymic injection group (group E). Rabbits' CSF was drained in group B; was drained and injected PBS into thymus in group C; was drained and injected CSF into thymus in group D; and was injected brain homogenate in group E. Half of the rabbits in each group were phlebotomized on 1st, 3rd, 7th, and 14th days to observe the changes in IL-l, TGF-β by ELISA test, and CD4CD25 regulatory T cells ratio by flow cytometry, and in other animals brain tissues were taken on 7th day for exploring FasL expression by RT-PCR. The least significant difference (LSD) test was used to make paired comparisons; P < 0.05 was considered statistically significant.</p><p><b>RESULTS</b>The levels of FasL, TGF-β, and the ratios of CD4CD25 regulatory T cells in groups D and E were apparently higher than those in other three groups (P < 0.05). Likewise, the levels of IL-1 in these two groups were lower than the other three groups (P < 0.05). Moreover, the ratios of CD4CD25 regulatory T cells and the levels of TGF-β in groups B and C were higher than those in group A, but the level of IL-1 was lower than that in group A (P < 0.05). There was no significant difference between groups B and C, and groups D and E.</p><p><b>CONCLUSION</b>Thymic injection of CSF and brain homogenate may be able to reduce inflammation after SBI, so thymus immune tolerance may be a useful therapy to treat SBI.</p>
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Animals , Rabbits , Autoantigens , Brain , General Surgery , Brain Injuries , Therapeutics , Immune Tolerance , Physiology , Thymus Gland , Allergy and ImmunologyABSTRACT
Objective To observe whether rabbit blood leptin can leak into the brain after craniocerebral trauma (CCT),and to dynamically detect serum levels of leptin,growth hormone (GH),and insulinlike growth factor-1 (IGF-1),and leptin level in cerebrospinal fluid (CSF) after CCT.Methods The FITC labeled leptin was injected into blood vessels of 15 adult male rabbits after anesthesia.Then 9 rabbits underwent unilateral fluid percussive impact,while 6 rabbits underwent sham operation.Thirty minutes postoperatively,brain tissue was taken to make frozen sections which were used to observe fluorescence labeled leptin range.Thirty three adult male rabbits were randomly divided into serum group,serum-control group,CSF group and CSF-control group.Rabbits in serum group and CSF group received fluid percussive impact,while rabbits in serum-control group and CSF-control group were drilled a 7 mm window in skull.Rabbits in serum group and serum-control group were phlebotomized 2 ml at 1 d,3 d,7 d and 14 d after operation,and rabbits in CSF group and CSF-control group were extracted CSF 0.5 ml at the same time points.Then serum levels of leptin,GH,and IGF-1,and leptin level in CSF were tested by ELISA.Results The fluorescence imaging could be seen in the injured brain tissue of rabbits with CCT,which was more than those in brain tissue of rabbits receiving sham operation.Serum leptin levels of rabbits in serum group at each time point were higher than those in serum-control group.Serum levels of GH and IGF-1 and leptin level in CSF were higher in rabbits with CCT than those in rabbits without CCT at 1 d,3 d and 7 d after operation.Conclusion The blood leptin can leak into the brain after CCT,which can cause increase of blood GH and IGF-1.And the latter may be the endocrine factors promoting fracture healing after CCT.
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ObjectiveTo investigate the impacts of neural stem cells (NSCs) transplantation on spinal pathology and ultrastructure after spinal cord injury (SCI) in rats and probe into the protective role of tacrolimus (FK506) on neural regeneration.MethodsCompressive SCI at T8 was induced in the adult SD rats,which were randomly assigned to the control group,FK506 group,NSCs group and NSCs + FK506 group.The differences of neural regeneration in each group were compared at days 7,14,28 and 56 after injury by motor evoked potentials ( MEP),HE staining,immunohistochemical staining,ultrastructure observation and image analysis of the myelinated fiber. ResultsThe MEP latency in the NSCs + FK506 group was significantly shorter than that in other groups at day 28 ( P ＜ 0.05 ).HE staining revealed that only local necrosis presented in the NSCs + FK506 group at day 56.More BrdU and NF-200 positive cells were detected with immunohistochemical staining in the other three groups as compared with the control group.Moreover,the positive cells in the NSCs + FK506 group also outnumbered the FK506 group and NSCs group.Electron microscope scan showed edema under the membrane of large myelin sheath in the control group,and classic new myelin sheath and neuraxis in the NSCs + FK506 group at day 56.The regeneration of the nerve fiber in the NSCs + FK506 group was better than that of other three groups (P ＜0.01 ).ConclusionAfter NSCs transplantation for SCI rats,the early combination use of FK506 can improve the pathology and ultrastructure of the regenerative nerve fiber and is conducive to nerve regeneration.
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ObjectiveTo investigate the curative effect of neural stem cells (NSCs) transplantation combined with monosialotetrahexosyl ganglioside (GMi) in treatment of acute spinal cord injury in rats.MethodsCompressive spinal cord injury model at T8 segment was established in the adult SD rats that were then randomly divided into three groups, ie, control group, NSCs transplantation group and NSCs + GM1 group.Continuous observation was performed at 1,2, 4 and 8 weeks.Functional neurological recovery of the injured spinal cord was evaluated with motor function scale, pathology, transmission electron microscopy and somatosensory evoked potential (SEP).ResultsThe motor function of the lower extremities was recovered at different degrees in three groups.While the motor function recovery level of the animals and the positive staining cells of the calcitonin gene-related peptide (CGRP) in the NSCs + GM1 group were higher than those in the other two groups at 4 and 8 weeks (P ＜ 0.01).Compared with control group and NSCs group, focal necrosis and small vessel regeneration were observed only in the center of the injured segment in the NSCs + GM1 group at 8 weeks.Electron microscope scan showed edema under the membrane of the large myelin sheath in the control group, much intact myelin sheath, well-differentiated neurons and many kinds of synapse vesicles in the NSCs + GM1 group.The latent period of SEP was shortened markedly in the NSCs + GM1 group two weeks after transplantation (P ＜0.05).The latent period shortening was apparent in the NSCs group at 4 and 8 weeks after transplantation but was still longer than that in the control group.ConclusionsTransplantation of neural stem cells combined with use of GM1 can protect the nervous tissues after spinal cord injury, when GM1 reconstructs the spinal cord through promoting differentiation of the transplanted stem cells and linking with the host cells.
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Objective To observe the effect of tacrolimus(FK506)in promoting repair of the injured spinal cord pathway after neural stem cell transplantation in rats. Methods A neurysm clip was used to compress the T8 spinal cord segment of SD rats under microscope to establish model of spinal cord injury.The rats were randomly divided into three groups seven days after injury,ie,control group (injection of normal saline at the injury center),transplantation group(injection of neural stem cells,NSCs,at the injury center),FK506 group(injection of NSCs at the injury center plus 7 days of intrapernerve conduction was compared by using the Basso-Beatfle-Bresnahan (BBB) scale,BDA tracing,somatosensory evoked potential(SEP)and motor evoked potentials(MEP)monitoring at 1,2,4 and 8weeks. Results The motor function of the hind limb after injury was recovered in various degrees with time,with the most significant recovery at 4 weeks.The BBB score reached 6,the maximum at 8 weeks.BDA tracing showed that some nerve fibers were found crossing the injured center of the spinal cord one week later in FK506 group and cell transplantation group,that BDA-positive labeled corticospinal tract fibets were seen across the injury site in all groups by the end ofthe eight weeks.In the FKS06 group,the regeneration could be observed even as 1.7 cm away from tlle injury center.SEP latency was significantly shorter in the FK506 group after two weeks(P<0.05)and the MEP latency in the FK506 group was shortened significantly at four weeks compared with the other groups(P<0.05),indicating that the immunosuppressants could promote the recovery of the injured spihal cord,shorten the latency of SEP and MEP，improve SEP at early stage and MEP at late stage．Conclusions Systemic application immuno suppressive agents FK506 plays an important role in neuroprotection and neurotrophy，which promotes the repair of the injured spinal cord after neural stem cell transplantation．
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Objective To study the expressions of erythmpoietin(EPO)and its receptors(EPOR)in the injured brain tissue ofthe rats with traumatic brain injury(TBI).Methods A total of78 SD rats were randomly divided into three groups including control group(six rats),sham group(36rats) and fluid percussion injury group(36 rats).The rats were sacrificed at 6,24 hours,3,5,7 and 14days after TBI in the sham group and the fluid percussion injury group(six rats at each time point).Then,the injured brain tissues were removed for observation of the mRNA and protein expressions of EPO and EPOR by meaDiB of real-time PCR and Western blot. Results The expression of EPO was increased at 24 hours and reached the peak at day 3 after TBI.The hish expression level of EPO could maintain for two days or so.began to decrease at day 7 and recovered to normal at day 14 after Till.While the expression of EPOR reached the peak at 24 hours after TBI and maintained hish level at day14. Conclusions The expressions of EPO and EPOR show increase within 24 hours after TBI.In fact,the expressions of both factors are not in consistency,with more transient expression of EPO.
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Aim To investigate the changes of intracellular calcium in primary cultured neurons after fluid percussion injury under the effects of cerebrolysin.Methods The neurons of rats were divided into: normal group,FPI group and cerebrolysin group(0 h and 1 h treatment after fluid percussion injury(FPI)).The intracellular calcium([Ca2+]i) at rats neurons in 24 h and 48 h postinjury were measured by using the laser scanning confocal microscope under calcium fluorescent indicator Fluo-3/AM.Results The [Ca2+]i at rats neurons were markedly increased after 24 h postinjury compared with normal neurons and maintained the higher level after 48 h.Cerebrolysin,whenever added at 0h or 1h after FBI,could significantly decrease the rise of [Ca2+]i on 24 h postinjury,which only happened in 48 h postinjury by 1 h treatment after FPI.Conclusion Cerebrolysin has the protective effects on primary cultured rat cortical neurons of rats and has the time-window treatment.