This article presents a case of a patient with relapsed esthesioneuroblastoma (ENB), an aggressive rare tumor that arises from the specialized sensory epithelial olfactory cells in the skull base area, which was initi...This article presents a case of a patient with relapsed esthesioneuroblastoma (ENB), an aggressive rare tumor that arises from the specialized sensory epithelial olfactory cells in the skull base area, which was initially treated with endoscopic surgery, followed by adjuvant radiotherapy. After local relapse, new surgical approaches and subsequent lines of platin-based chemotherapy were performed. A PET-CT with <sup>68</sup>GALIUM DOTATATOC (PET-DOTATOC) showed intense uptake of disease, compatible with the presence of somatostatin receptors, in the face, nodes, liver, bones, and meningeal area. Treatment with 4 cycles of <sup>177</sup>Lutetium-Dotatate was performed, followed by maintenance octreotide, with a major radiological and clinical response that is lasting more than 1 year after treatment. This article describes a rare case of a skull-base tumor, with multiple recurrences, in which disease control was achieved with a targeted Peptide Receptor Radionuclide Therapy (PRRT) with <sup>177</sup>Lutetium-Dotatate, and discusses factors that could influence the incorporation of this form of therapy. Previous case reports proved the potential efficacy of this therapy usually given for low-grade neuroendocrine tumors and will be carefully reviewed.展开更多
This paper presents a case of an olfactory neuroblastoma, treated with minimally invasive endoscopic resection, followed by adjuvant radiotherapy and critically reviews the current literature with regard to diagnosis ...This paper presents a case of an olfactory neuroblastoma, treated with minimally invasive endoscopic resection, followed by adjuvant radiotherapy and critically reviews the current literature with regard to diagnosis and management of such malignancies. Olfactory neuroblastoma is considered to be an uncommon malignancy of the nasal cavity. The tumor arises from the specialized sensory epithelial olfactory cells, normally situated at the upper part of the nasal cavity, including the superior nasal concha, the roof of the nose and the cribriform plate. The imaging modality of choice is computed tomography and magnetic resonance imaging. Combination of surgery and radiotherapy is considered to be the standard of care for primary site disease by the majority of researchers. Combined transfacial and neurosurgical conventional approaches are adopted in most cases, mainly due to the endocranial extension and the close anatomic relationship of esthesioneuroblastomas with the ethmoid roof and cribriform plate. However, recent literature supports that endoscopic resection correlates with similar oncologic control rates, compared with open surgery, when basic oncologic surgical principles are maintained.展开更多
Esthesioneuroblastoma is a malignant tumor, arising in the upper nasal cavity, that could spread to the frontal lobe of the brain as well as metastasize to the lymph nodes. Due to the low incidence of this tumor, FDA-...Esthesioneuroblastoma is a malignant tumor, arising in the upper nasal cavity, that could spread to the frontal lobe of the brain as well as metastasize to the lymph nodes. Due to the low incidence of this tumor, FDA-approved treatment modalities do not exist and clinical trials have not been performed. We present an interesting case of a 66-year-old female, diagnosed with Kadish stage B esthesioneuroblastoma and stage IIA nonsmall cell carcinoma of the lung, who benefited from our treatment. Both malignancies were diagnosed in 2002 at which time the patient consented to undergo left upper lobectomy for her lung cancer, but she refused the craniofacial resection and radiation therapy recommended for treatment of her esthesioneuroblastoma. From 2003 to 2004 she received treatment at the Burzynski Clinic with oral sodium phenylbutyrate (0.2 g/kg/day). She tolerated the treatment very well without significant adverse events. Gradual reduction in her tumor size was confirmed by repeat MRIs. From treatment start in March 2003 to December 2003 her tumor decreased by 40%. Subsequent MRI from March 2004 revealed increased tumor size, which, however, was still a 13% reduction from the baseline MRI. What is important to mention is that in addition to shrinkage of the esthesioneuroblastoma, the patient obtained the clinical benefit of 3.5-years longer survival than was predicted for her lung cancer—whereas the median survival for a patient with stage IIA adenocarcinoma of the left upper lobe of the lung is approximately two years, our patient survived more than five and a half years. The effect of phenylbutyrate (PB) and its metabolite phenylacetate on neuroblastoma and lung cancer is documented by numerous preclinical studies and is also evident in this case. It is proposed that the activity of these two compounds is mediated through increased expression of the p21 tumor suppressor gene. p21 is a strong inhibitor of cyclin-D and cyclin-dependent kinase 4, which contribute to undifferentiated phenotype in neuroblastoma and are instrumental in cell cycle progression from G1 to S phase. It is hoped that future research and combination of PB with other chemotherapeutic and targeted agents will provide better control of esthesioneuroblastoma and lung cancer.展开更多
BACKGROUND Neuroblastoma(NB)is one of the most common malignancies in children.Metastasis in NB is not uncommon.However,nasal metastases are rare.Here,we reported two pediatric cases of nasal metastases.CASE SUMMARY C...BACKGROUND Neuroblastoma(NB)is one of the most common malignancies in children.Metastasis in NB is not uncommon.However,nasal metastases are rare.Here,we reported two pediatric cases of nasal metastases.CASE SUMMARY Case 1 was a 3-year-old boy without a history of NB.Case 2 was a 10-year-old girl who had a history of NB for 6 years.Both of them presented with symptoms of nasal and sinus masses such as epistaxis or discharge from the nose.The radiologic imaging results revealed masses in the nasal cavity or nasopharynx in both cases and a mass in the right adrenal gland of case 1.The pathologic examination of biopsy samples of their nasal masses revealed“small round bluecell tumor”along with abundant vascular fibrous septa.The tumor cells expressed synaptophysin,cluster of differentiation 56,chromogranin A,paired like homeobox protein 2B and a very high Ki67 index in both case but were negative for vimentin,desmin,leucocyte common antigen and cytokeratin.Myelocytomatosis viral related oncogene,neuroblastoma derived(MYCN)amplification was detected in both cases.Finally,the two cases were diagnosed as nasal metastases from NB based on the clinical and pathologic findings.The two patients affected by NB were>18 mo old,the primary tumor location was adrenal gland,and they presented with multiple metastases.CONCLUSION It is difficult to differentiate between metastatic NB in the nose and olfactory neuroblastoma in the absence of a history of NB.Paired like homeobox protein 2B can play an important role in the diagnosis and differential diagnosis of this disease.展开更多
Olfactory neuroblastoma (esthesioneuroblastoma, ЕNB) is a rare tumor arising from the olfactory neuroepithelium. We report a case of ЕNB located in inferior nasal concha, combined with thyroid gland carcinoma and ga...Olfactory neuroblastoma (esthesioneuroblastoma, ЕNB) is a rare tumor arising from the olfactory neuroepithelium. We report a case of ЕNB located in inferior nasal concha, combined with thyroid gland carcinoma and gastrointestinal stromal carcinoma in a 77-year-old man. The tumor was resected endonasally. When the final diagnosis of olfactory neuroblastoma was confirmed by histopathologic examination and immunohistochemical staining, the PET/CT examination was performed. The imaging revealed a small focus of a moderately increased cancer activity in the thyroid region. A gastrointestinal stromal carcinoma was detected one year after the resection of the thyroid gland. We discuss the clinical appearance of ENB, staging systems, diagnosis and management. During the endonasal surgery, ENB was removed entirely. Seven days after operation, in order to monitor the postoperative result, PET/CT was performed and a papillary thyroid cancer was detected. One year after the thyroid surgery, gastroendoscopy showed a neoplastic formation in the stomach. In conclusion, we state that when identified as aggressive tumors such as ENB, it is necessary to provide regular examinations in order to detect distant ENB metastases or other neoplastic localisations.展开更多
This study investigated the effects of small interfering RNA (siRNA)-mediated silencing of chemokine receptor 4 (CXCR4) on the invasion capacity of human neuroblastoma cell line SH-SY5Y in vitro. Three siRNAs targ...This study investigated the effects of small interfering RNA (siRNA)-mediated silencing of chemokine receptor 4 (CXCR4) on the invasion capacity of human neuroblastoma cell line SH-SY5Y in vitro. Three siRNAs targeting CXCR4 were chemically synthesized and individually transfected into SH-SY5Y cells. Expression of CXCR4 mRNA and protein was signiifcantly sup-pressed in transfected cells by all three sequence-speciifc siRNAs compared with control groups. Furthermore, the invasion capacity of SH-SY5Y cells was signiifcantly decreased following trans-fection with CXCR4-speciifc siRNA compared with the control groups. These data demonstrate that down-regulation of CXCR4 can inhibit in vitro invasion of neuroblastoma.展开更多
A body of evidence suggests that ethanol can lead to damage of neuronal cells. However, the mechanism underlying the ethanol-induced damage of neuronal cells remains unclear. The role of mitogen-activated protein kina...A body of evidence suggests that ethanol can lead to damage of neuronal cells. However, the mechanism underlying the ethanol-induced damage of neuronal cells remains unclear. The role of mitogen-activated protein kinases in ethanol-induced damage was investigated in SK-N-SH neuroblastoma cells. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide cell viability assay, DNA fragmentation detection, and flow cytometric analysis showed that ethanol induced apoptotic cell death and cell cycle arrest, characterized by increased caspase-3 activity, DNA fragmentation, nuclear disruption, and G1 arrest of cell cycle of the SK-N-SH neuroblastoma cells. In addition, western blot analysis indicated that ethanol induced a lasting increase in c-Jun N-terminal protein kinase activity and a transient increase in p38 kinase activity of the neuroblastoma cells. c-Jun N-terminal protein kinase or p38 kinase inhibitors significantly reduced the ethanol-induced cell death. Ethanol also increased p53 phosphorylation, followed by an increase in p21 tumor suppressor protein and a decrease in phospho-Rb (retinoblastoma) protein, leading to alterations in the expressions and activity of cyclin dependent protein kinases. Our results suggest that ethanol mediates apoptosis of SK-N-SH neuroblastoma cells by activating p53-related cell cycle arrest possibly through activation of the c-Jun N-terminal protein kinase-related cell death pathway.展开更多
OBJECTIVE: To evaluate the effects of olfactory ensheathing cell transplantation on functional recovery of rats with complete spinal cord transection. DATA SOURCES: A computer-based online search of Medline (1989-2...OBJECTIVE: To evaluate the effects of olfactory ensheathing cell transplantation on functional recovery of rats with complete spinal cord transection. DATA SOURCES: A computer-based online search of Medline (1989-2013), Embase (1989- 2013), Cochrane library (1989-2013), Chinese Biomedical Literature Database (1989-2013), China National Knowledge Infrastructure (1989-2013), VIP (1989-2013), Wanfang databases (1989-2013) and Chinese Clinical Trial Register was conducted to collect randomized controlled trial data regarding olfactory ensheathing cell transplantation for the treatment of complete spinal cord transection in rats. SELECTION CRITERIA: Randomized controlled trials investigating olfactory ensheathing cell transplantation and other transplantation methods for promoting neurological functional recov- ery of rats with complete spinal cord transection were included in the analysis. Meta analysis was conducted using RevMan 4.2.2 software. MAIN OUTCOME MEASURES: Basso, Beattie and Bresnahan scores of rats with complete spinal cord transection were evaluated in this study. RESULTS: Six randomized controlled trials with high quality methodology were included. Meta analysis showed that Basso, Beattie and Bresnahan scores were significantly higher in the olfacto- ry ensheathing cell transplantation group compared with the control group (WMD = 3.16, 95% (21 (1.68, 4.65); P 〈 0.00001). CONCLUSION: Experimental studies have shown that olfactory ensheathing cell transplantation can promote the functional recovery of motor nerves in rats with complete spinal cord transection.展开更多
Olfactory bulb tissue transplantation inhibits P2X2/3 receptor-mediated neuropathic pain. However, the olfactory bulb has a complex cellular composition, and the mechanism underlying the action of purified transplante...Olfactory bulb tissue transplantation inhibits P2X2/3 receptor-mediated neuropathic pain. However, the olfactory bulb has a complex cellular composition, and the mechanism underlying the action of purified transplanted olfactory ensheathing cells(OECs) remains unclear. In the present study, we microencapsulated OECs in alginic acid, and transplanted free and microencapsulated OECs into the region surrounding the injured sciatic nerve in rat models of chronic constriction injury. We assessed mechanical nociception in the rat models 7 and 14 days after surgery by measuring paw withdrawal threshold, and examined P2X2/3 receptor expression in L4–5 dorsal root ganglia using immunohistochemistry. Rats that received free and microencapsulated OEC transplants showed greater withdrawal thresholds than untreated model rats, and weaker P2X2/3 receptor immunoreactivity in dorsal root ganglia. At 14 days, paw withdrawal threshold was much higher in the microencapsulated OEC-treated animals. Our results confirm that microencapsulated OEC transplantation suppresses P2X2/3 receptor expression in L4–5 dorsal root ganglia in rat models of neuropathic pain and reduces allodynia, and also suggest that transplantation of microencapsulated OECs is more effective than transplantation of free OECs for the treatment of neuropathic pain.展开更多
Olfactory ensheathing cells from the olfactory bulb and olfactory mucosa have been found to increase axonal sprouting and pathfinding and promote the recovery of vibrissae motor performance in facial nerve transection...Olfactory ensheathing cells from the olfactory bulb and olfactory mucosa have been found to increase axonal sprouting and pathfinding and promote the recovery of vibrissae motor performance in facial nerve transection injured rats. However, it is not yet clear whether olfactory ensheathing cells promote the reparation of facial nerve defects in rats. In this study, a collagen sponge and silicone tube neural conduit was implanted into the 6-mm defect of the buccal branch of the facial nerve in adult rats. Olfactory ensheathing cells isolated from the olfactory bulb of newborn Sprague-Dawley rats were injected into the neural conduits connecting the ends of the broken nerves, the morphology and function of the regenerated nerves were compared between the rats implanted with olfactory ensheathing cells with the rats injected with saline. Facial paralysis was assessed. Nerve electrography was used to measure facial nerve-induced action potentials. Visual inspection, anatomical microscopy and hematoxylin-eosin staining were used to assess the histomorphology around the transplanted neural conduit and the morphology of the regenerated nerve. Using fluorogold retrograde tracing, toluidine blue staining and lead uranyl acetate staining, we also measured the number of neurons in the anterior exterior lateral facial nerve motor nucleus, the number of myelinated nerve fibers, and nerve fiber diameter and myelin sheath thickness, respectively. After surgery, olfactory ensheathing cells decreased facial paralysis and the latency of the facial nerve-induced action potentials. There were no differences in the general morphology of the regenerating nerves between the rats implanted with olfactory ensheathing cells and the rats injected with saline. Between-group results showed that olfactory ensheathing cell treatment increased the number of regenerated neurons, improved nerve fiber morphology, and increased the number of myelinated nerve fibers, nerve fiber diameter, and myelin sheath thickness. In conclusion, implantation of olfactory ensheathing cells can promote regeneration and functional recovery after facial nerve damage in rats.展开更多
Background:Historically sinonasal malignancies were always addressed via open craniofacial surgery for an oncologic resection.Increasingly esthesioneuroblastomas are excised using an exclusively endoscopic approach,ho...Background:Historically sinonasal malignancies were always addressed via open craniofacial surgery for an oncologic resection.Increasingly esthesioneuroblastomas are excised using an exclusively endoscopic approach,however,the rarity of this disease limits the availability of long-term and large scale outcomes data.Objective:The primary objective is to evaluate the treatment modalities used and the overall survival of patients with esthesioneuroblastoma managed with exclusively endoscopic surgery.Methods:In accordance with PRISMA guidelines,PubMed was queried to identify studies describing outcomes associated with endoscopic management of esthesioneuroblastomas.Results:Forty-four out of 2462 articles met inclusion criteria,totaling 399 patients with esthesioneuroblastoma treated with an exclusively endoscopic approach.Seventy-two patients(18.0%)received adjuvant chemotherapy and 331 patients(83.0%)received postoperative radiation therapy.The average age was 50.6 years old(range 6-83).Of the 399 patients,57(16.6%)were Kadish stage A,121(35.2%)were Kadish stage B,145(42.2%)were Kadish stage C,and 21(6.1%)were Kadish stage D.Pooled analysis demonstrated that 66.0%of patients had Hyams histologic GradeⅠorⅡ,while 34.0%of patients had GradeⅢorⅣdisease.Negative surgical margins were achieved in 86.9%of patients,and recurrence was identified in 10.3%of patients.Of those with 5-year follow-up,reported overall survival was 91.1%.Conclusion:Exclusively endoscopic surgery for esthesioneuroblastoma is performed for a wide range of disease stages and grades,and the majority of these patients are also treated with adjuvant chemotherapy or radiation therapy.Reported overall recurrence rate is 10.3%and 5-year survival is 91.1%.展开更多
Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ische...Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.展开更多
The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volum...The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volume and promote proliferation and differentiation of neural stem cells in the hippocampus and lateral ventricles. However, there is a lack of studies on whether total saponins of Panax notoginsertg have potential benefits on immature neuroblasts in the olfactory bulb following ischemia and reperfusion. This study established a rat model of global cerebral ischemia and reperfusion using four-vessel occlusion. Rats were administered total sa- ponins of Panax notoginseng at 75 mg/kg intraperitoneally 30 minutes after ischemia then once a day, for either 7 or 14 days. Total saponins of Panax notoginseng enhanced the number of dou- blecortin (DCX)+ neural progenitor ceils and increased co-localization of DCX with neuronal nuclei and phosphorylated cAMP response element-binding/DCX+ neural progenitor cells in the olfactory bulb at 7 and 14 days post ischemia. These findings indicate that following global brain ischemia/reperfusion, total saponins of Panax notoginseng promote differentiation of DCX+ cells expressing immature neuroblasts in the olfactory bulb and the underlying mechanism is related to the activation of the signaling pathway of cyclic adenosine monophosphate response element binding protein.展开更多
Forty-three patients with chronic spinal cord injury for over 6 months were transplanted with bryonic olfactory ensheathing cells, 2-4 × 106, into multiple sites in the injured area under the sur-gical microscope...Forty-three patients with chronic spinal cord injury for over 6 months were transplanted with bryonic olfactory ensheathing cells, 2-4 × 106, into multiple sites in the injured area under the sur-gical microscope. The sympathetic skin response in patients was measured with an electromyo-graphy/evoked potential instrument 1 day before transplantation and 3-8 weeks after trans-tion. Spinal nerve function of patients was assessed using the American Spinal Injury Association impairment scale. The sympathetic skin response was elicited in 32 cases before olfactory en-sheathing celltransplantation, while it was observed in 34 cases after transplantation. tantly, sympathetic skin response latency decreased significantly and amplitude increased cantly after transplantation. Transplantation of olfactory ensheathing cells also improved American Spinal Injury Association scores for movement, pain and light touch. Our findings indicate that factory ensheathing celltransplantation improves motor, sensory and autonomic nerve functions in patients with chronic spinal cord injury.展开更多
Hyperhomocysteinemia has been shown to be associated with neurodegenerative diseases; however, lesions or histological changes and mechanisms underlying homocysteine-induced injury in olfactory bulb neurons remain unc...Hyperhomocysteinemia has been shown to be associated with neurodegenerative diseases; however, lesions or histological changes and mechanisms underlying homocysteine-induced injury in olfactory bulb neurons remain unclear. In this study, hyperhomocysteinemia was induced in apolipoprotein E-deficient mice with 1.7% methionine. Pathological changes in the olfactory bulb were observed through hematoxylin-eosin and Pischingert staining. Cell apoptosis in the olfactory bulb was determined through terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Transmission electron microscopy revealed an abnormal ultrastructure of neurons. Furthermore, immunoreactivity and expression of the hairy enhancer of the split 1 (Hesl) and Hess were measured using immunohistochemistry, immunofluorescence, and western blot assay. Our results revealed no significant structural abnormality in the ol- factory bulb of hyperhomocysteinemic mice. However, the number of TUNEL-positive cells increased in the olfactory bulb, lipofuscin and vacuolization were visible in mitochondria, and the expression of Hes1 and Hes5 decreased. These findings confirm that hyperhomocyste- inemia induces injury in olfactory bulb neurons by downregulating Hes1 and Hes5 expression.展开更多
BACKGROUND: Olfactory ensheathing cell (OEC) transplantation promotes repair of spinal cord injury. Neural regeneration inhibits binding of the myelin protein Nogo to its receptor (NgR), activates downstream inhi...BACKGROUND: Olfactory ensheathing cell (OEC) transplantation promotes repair of spinal cord injury. Neural regeneration inhibits binding of the myelin protein Nogo to its receptor (NgR), activates downstream inhibitory signal RhoA, and leads to axonal degeneration. OBJECTIVE: To determine the relationship between OECs transplantation for spinal cord injury and NogoA, NgR, and RhoA protein expression in the damaged zone. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed from September 2006 to May 2007 at the Key Laboratory of Environment and Genes in Xi'an Jiaotong University School of Medicine, China. MATERIALS: OECs were harvested from healthy, adult, male, Sprague Dawley rats aged 6 months. Mouse anti-rat NogoA, NgR, and RheA monoclonal antibodies were utilized for detection. METHODS: A total of 40 adult Sprague Dawley rats were randomly assigned to four groups: normal, model, OECs, and DF12, with 10 animals in each group. Transverse section spinal cord injury was established in the OECs and DF12 groups, followed by injection of 1μL OECs suspension (1×10^8/mL) or equivalent DF12 medium at 1 mm above and below the injury site. MAIN OUTCOME MEASURES: Immunohistochemistry and Western blot were utilized to detect NogoA, NgR, and RhoA expression in the spinal cord injury lesions. Morphological changes were observed by argyrophilia staining, and lower extremity function of the animals was assessed using Basso, Beattie, and Bresnahan scores. RESULTS: Eight weeks following OECs transplantation, a significant increase in new axons was observed in the OECs group, and nerve fibers crossed the injury site to repair spinal cord injury. Qualitative and quantitative results from the OECs group were superior to the model and DF12 groups. At 8 weeks after transplantation, Basso, Beattie, and Bresnahan scores were significantly greater in the OECs group compared with the model and DF12 groups (P 〈 0.01), but expression of NogoA, NgR, and RhoA protein was significantly decreased compared with the model and DF12 groups (P〈 0.05). CONCLUSION: OEC transplantation could inhibit NogoA, NgR, and RhoA expression in spinal cord injury lesions, thereby promoting repair of spinal cord injury.展开更多
OBJECTIVE: To identify global research trends in transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury. DATA RETRIEVAL: We performed a bibliometric analysis of st...OBJECTIVE: To identify global research trends in transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury. DATA RETRIEVAL: We performed a bibliometric analysis of studies on transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury published from 2002 to 2011 and retrieved from the Web of Science, using the key words spinal cord injury along with either neural stem cell, Schwann cell or olfactory ensheathing cell. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on neural stem cells, Schwann cells or olfactory ensheathing cells for spinal cord injury indexed in the Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial materials and news items; and (c) published between 2002 and 2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) corrected papers. MAIN OUTCOME MEASURES: (1)Annual publication output, distribution by journal, distribution by institution and top-cited articles on neural stem cells; (2) annual publication output, distribution by journal, distribution by institution and top-cited articles on Schwann cells; (3) annual publication output, distribution by journal, distribution by institution and top-cited articles on olfactory ensheathing cells. RESULTS: This analysis, based on articles indexed in the Web of Science, identified several research trends among studies published over the past 10 years in transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury. The number of publications increased over the 10-year period examined. Most papers appeared in journals with a focus on neurology, such as Journal of Neurotrauma, Experimental Neurology and Gila. Research institutes publishing on the use of neural stem cells to repair spinal cord injury were mostly in the USA and Canada. Those publishing on the use of Schwann cells were mostly in the USA and Canada as well. Those publishing on the use of olfactory ensheathing cells were mostly in the UK, the USA and Canada. CONCLUSION: On the basis of the large number of studies around the world, cell transplantation has proven to be the most promising therapeutic approach for spinal cord injury.展开更多
Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relations...Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relationship between neural stem cell status in the subventricular zone and olfactory function in rats with diabetes mellitus.Streptozotocin was injected through the femoral vein to induce type 1 diabetes mellitus in Sprague-Dawley rats.Two months after injection,olfactory sensitivity was decreased in diabetic rats.Meanwhile,the number of Brd U-positive and Brd U+/DCX+double-labeled cells was lower in the subventricular zone of diabetic rats compared with agematched normal rats.Western blot results revealed downregulated expression of insulin receptorβ,phosphorylated glycogen synthase kinase 3β,and β-catenin in the subventricular zone of diabetic rats.Altogether,these results indicate that diabetes mellitus causes insulin deficiency,which negatively regulates glycogen synthase kinase 3β and enhances β-catenin degradation,with these changes inhibiting neural stem cell proliferation.Further,these signaling pathways affect proliferation and differentiation of neural stem cells in the subventricular zone.Dysfunction of subventricular zone neural stem cells causes a decline in olfactory bulb structural plasticity and impairs olfactory sensitivity in diabetic rats.展开更多
文摘This article presents a case of a patient with relapsed esthesioneuroblastoma (ENB), an aggressive rare tumor that arises from the specialized sensory epithelial olfactory cells in the skull base area, which was initially treated with endoscopic surgery, followed by adjuvant radiotherapy. After local relapse, new surgical approaches and subsequent lines of platin-based chemotherapy were performed. A PET-CT with <sup>68</sup>GALIUM DOTATATOC (PET-DOTATOC) showed intense uptake of disease, compatible with the presence of somatostatin receptors, in the face, nodes, liver, bones, and meningeal area. Treatment with 4 cycles of <sup>177</sup>Lutetium-Dotatate was performed, followed by maintenance octreotide, with a major radiological and clinical response that is lasting more than 1 year after treatment. This article describes a rare case of a skull-base tumor, with multiple recurrences, in which disease control was achieved with a targeted Peptide Receptor Radionuclide Therapy (PRRT) with <sup>177</sup>Lutetium-Dotatate, and discusses factors that could influence the incorporation of this form of therapy. Previous case reports proved the potential efficacy of this therapy usually given for low-grade neuroendocrine tumors and will be carefully reviewed.
文摘This paper presents a case of an olfactory neuroblastoma, treated with minimally invasive endoscopic resection, followed by adjuvant radiotherapy and critically reviews the current literature with regard to diagnosis and management of such malignancies. Olfactory neuroblastoma is considered to be an uncommon malignancy of the nasal cavity. The tumor arises from the specialized sensory epithelial olfactory cells, normally situated at the upper part of the nasal cavity, including the superior nasal concha, the roof of the nose and the cribriform plate. The imaging modality of choice is computed tomography and magnetic resonance imaging. Combination of surgery and radiotherapy is considered to be the standard of care for primary site disease by the majority of researchers. Combined transfacial and neurosurgical conventional approaches are adopted in most cases, mainly due to the endocranial extension and the close anatomic relationship of esthesioneuroblastomas with the ethmoid roof and cribriform plate. However, recent literature supports that endoscopic resection correlates with similar oncologic control rates, compared with open surgery, when basic oncologic surgical principles are maintained.
文摘Esthesioneuroblastoma is a malignant tumor, arising in the upper nasal cavity, that could spread to the frontal lobe of the brain as well as metastasize to the lymph nodes. Due to the low incidence of this tumor, FDA-approved treatment modalities do not exist and clinical trials have not been performed. We present an interesting case of a 66-year-old female, diagnosed with Kadish stage B esthesioneuroblastoma and stage IIA nonsmall cell carcinoma of the lung, who benefited from our treatment. Both malignancies were diagnosed in 2002 at which time the patient consented to undergo left upper lobectomy for her lung cancer, but she refused the craniofacial resection and radiation therapy recommended for treatment of her esthesioneuroblastoma. From 2003 to 2004 she received treatment at the Burzynski Clinic with oral sodium phenylbutyrate (0.2 g/kg/day). She tolerated the treatment very well without significant adverse events. Gradual reduction in her tumor size was confirmed by repeat MRIs. From treatment start in March 2003 to December 2003 her tumor decreased by 40%. Subsequent MRI from March 2004 revealed increased tumor size, which, however, was still a 13% reduction from the baseline MRI. What is important to mention is that in addition to shrinkage of the esthesioneuroblastoma, the patient obtained the clinical benefit of 3.5-years longer survival than was predicted for her lung cancer—whereas the median survival for a patient with stage IIA adenocarcinoma of the left upper lobe of the lung is approximately two years, our patient survived more than five and a half years. The effect of phenylbutyrate (PB) and its metabolite phenylacetate on neuroblastoma and lung cancer is documented by numerous preclinical studies and is also evident in this case. It is proposed that the activity of these two compounds is mediated through increased expression of the p21 tumor suppressor gene. p21 is a strong inhibitor of cyclin-D and cyclin-dependent kinase 4, which contribute to undifferentiated phenotype in neuroblastoma and are instrumental in cell cycle progression from G1 to S phase. It is hoped that future research and combination of PB with other chemotherapeutic and targeted agents will provide better control of esthesioneuroblastoma and lung cancer.
文摘BACKGROUND Neuroblastoma(NB)is one of the most common malignancies in children.Metastasis in NB is not uncommon.However,nasal metastases are rare.Here,we reported two pediatric cases of nasal metastases.CASE SUMMARY Case 1 was a 3-year-old boy without a history of NB.Case 2 was a 10-year-old girl who had a history of NB for 6 years.Both of them presented with symptoms of nasal and sinus masses such as epistaxis or discharge from the nose.The radiologic imaging results revealed masses in the nasal cavity or nasopharynx in both cases and a mass in the right adrenal gland of case 1.The pathologic examination of biopsy samples of their nasal masses revealed“small round bluecell tumor”along with abundant vascular fibrous septa.The tumor cells expressed synaptophysin,cluster of differentiation 56,chromogranin A,paired like homeobox protein 2B and a very high Ki67 index in both case but were negative for vimentin,desmin,leucocyte common antigen and cytokeratin.Myelocytomatosis viral related oncogene,neuroblastoma derived(MYCN)amplification was detected in both cases.Finally,the two cases were diagnosed as nasal metastases from NB based on the clinical and pathologic findings.The two patients affected by NB were>18 mo old,the primary tumor location was adrenal gland,and they presented with multiple metastases.CONCLUSION It is difficult to differentiate between metastatic NB in the nose and olfactory neuroblastoma in the absence of a history of NB.Paired like homeobox protein 2B can play an important role in the diagnosis and differential diagnosis of this disease.
文摘Olfactory neuroblastoma (esthesioneuroblastoma, ЕNB) is a rare tumor arising from the olfactory neuroepithelium. We report a case of ЕNB located in inferior nasal concha, combined with thyroid gland carcinoma and gastrointestinal stromal carcinoma in a 77-year-old man. The tumor was resected endonasally. When the final diagnosis of olfactory neuroblastoma was confirmed by histopathologic examination and immunohistochemical staining, the PET/CT examination was performed. The imaging revealed a small focus of a moderately increased cancer activity in the thyroid region. A gastrointestinal stromal carcinoma was detected one year after the resection of the thyroid gland. We discuss the clinical appearance of ENB, staging systems, diagnosis and management. During the endonasal surgery, ENB was removed entirely. Seven days after operation, in order to monitor the postoperative result, PET/CT was performed and a papillary thyroid cancer was detected. One year after the thyroid surgery, gastroendoscopy showed a neoplastic formation in the stomach. In conclusion, we state that when identified as aggressive tumors such as ENB, it is necessary to provide regular examinations in order to detect distant ENB metastases or other neoplastic localisations.
基金supported by the National Natural Science Foundation of China,No.81272986the Natural Science Foundation of Shandong Province,No.ZR2011HZ002
文摘This study investigated the effects of small interfering RNA (siRNA)-mediated silencing of chemokine receptor 4 (CXCR4) on the invasion capacity of human neuroblastoma cell line SH-SY5Y in vitro. Three siRNAs targeting CXCR4 were chemically synthesized and individually transfected into SH-SY5Y cells. Expression of CXCR4 mRNA and protein was signiifcantly sup-pressed in transfected cells by all three sequence-speciifc siRNAs compared with control groups. Furthermore, the invasion capacity of SH-SY5Y cells was signiifcantly decreased following trans-fection with CXCR4-speciifc siRNA compared with the control groups. These data demonstrate that down-regulation of CXCR4 can inhibit in vitro invasion of neuroblastoma.
基金supported by a grant from Hallym University Medical Center Research Fund,No.01-2009-15
文摘A body of evidence suggests that ethanol can lead to damage of neuronal cells. However, the mechanism underlying the ethanol-induced damage of neuronal cells remains unclear. The role of mitogen-activated protein kinases in ethanol-induced damage was investigated in SK-N-SH neuroblastoma cells. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide cell viability assay, DNA fragmentation detection, and flow cytometric analysis showed that ethanol induced apoptotic cell death and cell cycle arrest, characterized by increased caspase-3 activity, DNA fragmentation, nuclear disruption, and G1 arrest of cell cycle of the SK-N-SH neuroblastoma cells. In addition, western blot analysis indicated that ethanol induced a lasting increase in c-Jun N-terminal protein kinase activity and a transient increase in p38 kinase activity of the neuroblastoma cells. c-Jun N-terminal protein kinase or p38 kinase inhibitors significantly reduced the ethanol-induced cell death. Ethanol also increased p53 phosphorylation, followed by an increase in p21 tumor suppressor protein and a decrease in phospho-Rb (retinoblastoma) protein, leading to alterations in the expressions and activity of cyclin dependent protein kinases. Our results suggest that ethanol mediates apoptosis of SK-N-SH neuroblastoma cells by activating p53-related cell cycle arrest possibly through activation of the c-Jun N-terminal protein kinase-related cell death pathway.
文摘OBJECTIVE: To evaluate the effects of olfactory ensheathing cell transplantation on functional recovery of rats with complete spinal cord transection. DATA SOURCES: A computer-based online search of Medline (1989-2013), Embase (1989- 2013), Cochrane library (1989-2013), Chinese Biomedical Literature Database (1989-2013), China National Knowledge Infrastructure (1989-2013), VIP (1989-2013), Wanfang databases (1989-2013) and Chinese Clinical Trial Register was conducted to collect randomized controlled trial data regarding olfactory ensheathing cell transplantation for the treatment of complete spinal cord transection in rats. SELECTION CRITERIA: Randomized controlled trials investigating olfactory ensheathing cell transplantation and other transplantation methods for promoting neurological functional recov- ery of rats with complete spinal cord transection were included in the analysis. Meta analysis was conducted using RevMan 4.2.2 software. MAIN OUTCOME MEASURES: Basso, Beattie and Bresnahan scores of rats with complete spinal cord transection were evaluated in this study. RESULTS: Six randomized controlled trials with high quality methodology were included. Meta analysis showed that Basso, Beattie and Bresnahan scores were significantly higher in the olfacto- ry ensheathing cell transplantation group compared with the control group (WMD = 3.16, 95% (21 (1.68, 4.65); P 〈 0.00001). CONCLUSION: Experimental studies have shown that olfactory ensheathing cell transplantation can promote the functional recovery of motor nerves in rats with complete spinal cord transection.
基金supported by the National Natural Science Foundation of China,No.81260190the Natural Science Foundation of Jiangxi Province of China,No.20132BAB205023+1 种基金a grant from the Science and Technology Research Program of Department of Education of Jiangxi Province in China,No.GJJ13159a grant from the Science and Technology Program of Department of Health of Jiangxi Province,No.20132019
文摘Olfactory bulb tissue transplantation inhibits P2X2/3 receptor-mediated neuropathic pain. However, the olfactory bulb has a complex cellular composition, and the mechanism underlying the action of purified transplanted olfactory ensheathing cells(OECs) remains unclear. In the present study, we microencapsulated OECs in alginic acid, and transplanted free and microencapsulated OECs into the region surrounding the injured sciatic nerve in rat models of chronic constriction injury. We assessed mechanical nociception in the rat models 7 and 14 days after surgery by measuring paw withdrawal threshold, and examined P2X2/3 receptor expression in L4–5 dorsal root ganglia using immunohistochemistry. Rats that received free and microencapsulated OEC transplants showed greater withdrawal thresholds than untreated model rats, and weaker P2X2/3 receptor immunoreactivity in dorsal root ganglia. At 14 days, paw withdrawal threshold was much higher in the microencapsulated OEC-treated animals. Our results confirm that microencapsulated OEC transplantation suppresses P2X2/3 receptor expression in L4–5 dorsal root ganglia in rat models of neuropathic pain and reduces allodynia, and also suggest that transplantation of microencapsulated OECs is more effective than transplantation of free OECs for the treatment of neuropathic pain.
基金supported by the Foundation for Military Medicine,China,No.BWS11J035(to JPF)the Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai of China,No.PWZxq2017-09(to XPC and JPF)
文摘Olfactory ensheathing cells from the olfactory bulb and olfactory mucosa have been found to increase axonal sprouting and pathfinding and promote the recovery of vibrissae motor performance in facial nerve transection injured rats. However, it is not yet clear whether olfactory ensheathing cells promote the reparation of facial nerve defects in rats. In this study, a collagen sponge and silicone tube neural conduit was implanted into the 6-mm defect of the buccal branch of the facial nerve in adult rats. Olfactory ensheathing cells isolated from the olfactory bulb of newborn Sprague-Dawley rats were injected into the neural conduits connecting the ends of the broken nerves, the morphology and function of the regenerated nerves were compared between the rats implanted with olfactory ensheathing cells with the rats injected with saline. Facial paralysis was assessed. Nerve electrography was used to measure facial nerve-induced action potentials. Visual inspection, anatomical microscopy and hematoxylin-eosin staining were used to assess the histomorphology around the transplanted neural conduit and the morphology of the regenerated nerve. Using fluorogold retrograde tracing, toluidine blue staining and lead uranyl acetate staining, we also measured the number of neurons in the anterior exterior lateral facial nerve motor nucleus, the number of myelinated nerve fibers, and nerve fiber diameter and myelin sheath thickness, respectively. After surgery, olfactory ensheathing cells decreased facial paralysis and the latency of the facial nerve-induced action potentials. There were no differences in the general morphology of the regenerating nerves between the rats implanted with olfactory ensheathing cells and the rats injected with saline. Between-group results showed that olfactory ensheathing cell treatment increased the number of regenerated neurons, improved nerve fiber morphology, and increased the number of myelinated nerve fibers, nerve fiber diameter, and myelin sheath thickness. In conclusion, implantation of olfactory ensheathing cells can promote regeneration and functional recovery after facial nerve damage in rats.
文摘Background:Historically sinonasal malignancies were always addressed via open craniofacial surgery for an oncologic resection.Increasingly esthesioneuroblastomas are excised using an exclusively endoscopic approach,however,the rarity of this disease limits the availability of long-term and large scale outcomes data.Objective:The primary objective is to evaluate the treatment modalities used and the overall survival of patients with esthesioneuroblastoma managed with exclusively endoscopic surgery.Methods:In accordance with PRISMA guidelines,PubMed was queried to identify studies describing outcomes associated with endoscopic management of esthesioneuroblastomas.Results:Forty-four out of 2462 articles met inclusion criteria,totaling 399 patients with esthesioneuroblastoma treated with an exclusively endoscopic approach.Seventy-two patients(18.0%)received adjuvant chemotherapy and 331 patients(83.0%)received postoperative radiation therapy.The average age was 50.6 years old(range 6-83).Of the 399 patients,57(16.6%)were Kadish stage A,121(35.2%)were Kadish stage B,145(42.2%)were Kadish stage C,and 21(6.1%)were Kadish stage D.Pooled analysis demonstrated that 66.0%of patients had Hyams histologic GradeⅠorⅡ,while 34.0%of patients had GradeⅢorⅣdisease.Negative surgical margins were achieved in 86.9%of patients,and recurrence was identified in 10.3%of patients.Of those with 5-year follow-up,reported overall survival was 91.1%.Conclusion:Exclusively endoscopic surgery for esthesioneuroblastoma is performed for a wide range of disease stages and grades,and the majority of these patients are also treated with adjuvant chemotherapy or radiation therapy.Reported overall recurrence rate is 10.3%and 5-year survival is 91.1%.
基金supported by the National Natural Science Foundation of China,No.82001604Guizhou Provincial Higher Education Science and Technology Innovation Team,No.[2023]072+1 种基金Guizhou Province Distinguished Young Scientific and Technological Talent Program,No.YQK[2023]040Guizhou Provincial Basic Research Program(Natural Science),No.ZK[2021]-368(all to LXiong),and Zunyi City Innovative Talent Team Training Plan,No.[2022]-2.
文摘Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.
基金supported by the Hunan Provincial Innovation Foundation for Postgraduate in China,No.CX2014B099(to XH)the Science Foundation of Hunan Provincial Education Department of China,No.11C1264(to FJD),13C958(to XH)
文摘The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volume and promote proliferation and differentiation of neural stem cells in the hippocampus and lateral ventricles. However, there is a lack of studies on whether total saponins of Panax notoginsertg have potential benefits on immature neuroblasts in the olfactory bulb following ischemia and reperfusion. This study established a rat model of global cerebral ischemia and reperfusion using four-vessel occlusion. Rats were administered total sa- ponins of Panax notoginseng at 75 mg/kg intraperitoneally 30 minutes after ischemia then once a day, for either 7 or 14 days. Total saponins of Panax notoginseng enhanced the number of dou- blecortin (DCX)+ neural progenitor ceils and increased co-localization of DCX with neuronal nuclei and phosphorylated cAMP response element-binding/DCX+ neural progenitor cells in the olfactory bulb at 7 and 14 days post ischemia. These findings indicate that following global brain ischemia/reperfusion, total saponins of Panax notoginseng promote differentiation of DCX+ cells expressing immature neuroblasts in the olfactory bulb and the underlying mechanism is related to the activation of the signaling pathway of cyclic adenosine monophosphate response element binding protein.
文摘Forty-three patients with chronic spinal cord injury for over 6 months were transplanted with bryonic olfactory ensheathing cells, 2-4 × 106, into multiple sites in the injured area under the sur-gical microscope. The sympathetic skin response in patients was measured with an electromyo-graphy/evoked potential instrument 1 day before transplantation and 3-8 weeks after trans-tion. Spinal nerve function of patients was assessed using the American Spinal Injury Association impairment scale. The sympathetic skin response was elicited in 32 cases before olfactory en-sheathing celltransplantation, while it was observed in 34 cases after transplantation. tantly, sympathetic skin response latency decreased significantly and amplitude increased cantly after transplantation. Transplantation of olfactory ensheathing cells also improved American Spinal Injury Association scores for movement, pain and light touch. Our findings indicate that factory ensheathing celltransplantation improves motor, sensory and autonomic nerve functions in patients with chronic spinal cord injury.
基金supported by the National Natural Science Foundation of China,No.81560084,81560208a grant from the Project of Superior Discipline Groups in Ningxia Medical University of China,No.XY201414
文摘Hyperhomocysteinemia has been shown to be associated with neurodegenerative diseases; however, lesions or histological changes and mechanisms underlying homocysteine-induced injury in olfactory bulb neurons remain unclear. In this study, hyperhomocysteinemia was induced in apolipoprotein E-deficient mice with 1.7% methionine. Pathological changes in the olfactory bulb were observed through hematoxylin-eosin and Pischingert staining. Cell apoptosis in the olfactory bulb was determined through terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Transmission electron microscopy revealed an abnormal ultrastructure of neurons. Furthermore, immunoreactivity and expression of the hairy enhancer of the split 1 (Hesl) and Hess were measured using immunohistochemistry, immunofluorescence, and western blot assay. Our results revealed no significant structural abnormality in the ol- factory bulb of hyperhomocysteinemic mice. However, the number of TUNEL-positive cells increased in the olfactory bulb, lipofuscin and vacuolization were visible in mitochondria, and the expression of Hes1 and Hes5 decreased. These findings confirm that hyperhomocyste- inemia induces injury in olfactory bulb neurons by downregulating Hes1 and Hes5 expression.
基金Doctoral Fund of Ministry of Education of China,No.20050698043
文摘BACKGROUND: Olfactory ensheathing cell (OEC) transplantation promotes repair of spinal cord injury. Neural regeneration inhibits binding of the myelin protein Nogo to its receptor (NgR), activates downstream inhibitory signal RhoA, and leads to axonal degeneration. OBJECTIVE: To determine the relationship between OECs transplantation for spinal cord injury and NogoA, NgR, and RhoA protein expression in the damaged zone. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed from September 2006 to May 2007 at the Key Laboratory of Environment and Genes in Xi'an Jiaotong University School of Medicine, China. MATERIALS: OECs were harvested from healthy, adult, male, Sprague Dawley rats aged 6 months. Mouse anti-rat NogoA, NgR, and RheA monoclonal antibodies were utilized for detection. METHODS: A total of 40 adult Sprague Dawley rats were randomly assigned to four groups: normal, model, OECs, and DF12, with 10 animals in each group. Transverse section spinal cord injury was established in the OECs and DF12 groups, followed by injection of 1μL OECs suspension (1×10^8/mL) or equivalent DF12 medium at 1 mm above and below the injury site. MAIN OUTCOME MEASURES: Immunohistochemistry and Western blot were utilized to detect NogoA, NgR, and RhoA expression in the spinal cord injury lesions. Morphological changes were observed by argyrophilia staining, and lower extremity function of the animals was assessed using Basso, Beattie, and Bresnahan scores. RESULTS: Eight weeks following OECs transplantation, a significant increase in new axons was observed in the OECs group, and nerve fibers crossed the injury site to repair spinal cord injury. Qualitative and quantitative results from the OECs group were superior to the model and DF12 groups. At 8 weeks after transplantation, Basso, Beattie, and Bresnahan scores were significantly greater in the OECs group compared with the model and DF12 groups (P 〈 0.01), but expression of NogoA, NgR, and RhoA protein was significantly decreased compared with the model and DF12 groups (P〈 0.05). CONCLUSION: OEC transplantation could inhibit NogoA, NgR, and RhoA expression in spinal cord injury lesions, thereby promoting repair of spinal cord injury.
基金supported by the Foundation of Science and Technology Development Program of Jilin Provincial Science and Technology Department,No.200905183
文摘OBJECTIVE: To identify global research trends in transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury. DATA RETRIEVAL: We performed a bibliometric analysis of studies on transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury published from 2002 to 2011 and retrieved from the Web of Science, using the key words spinal cord injury along with either neural stem cell, Schwann cell or olfactory ensheathing cell. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on neural stem cells, Schwann cells or olfactory ensheathing cells for spinal cord injury indexed in the Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial materials and news items; and (c) published between 2002 and 2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) corrected papers. MAIN OUTCOME MEASURES: (1)Annual publication output, distribution by journal, distribution by institution and top-cited articles on neural stem cells; (2) annual publication output, distribution by journal, distribution by institution and top-cited articles on Schwann cells; (3) annual publication output, distribution by journal, distribution by institution and top-cited articles on olfactory ensheathing cells. RESULTS: This analysis, based on articles indexed in the Web of Science, identified several research trends among studies published over the past 10 years in transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury. The number of publications increased over the 10-year period examined. Most papers appeared in journals with a focus on neurology, such as Journal of Neurotrauma, Experimental Neurology and Gila. Research institutes publishing on the use of neural stem cells to repair spinal cord injury were mostly in the USA and Canada. Those publishing on the use of Schwann cells were mostly in the USA and Canada as well. Those publishing on the use of olfactory ensheathing cells were mostly in the UK, the USA and Canada. CONCLUSION: On the basis of the large number of studies around the world, cell transplantation has proven to be the most promising therapeutic approach for spinal cord injury.
基金partly supported by the National Natural Science Foundation of China,No.81370448,81570725
文摘Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relationship between neural stem cell status in the subventricular zone and olfactory function in rats with diabetes mellitus.Streptozotocin was injected through the femoral vein to induce type 1 diabetes mellitus in Sprague-Dawley rats.Two months after injection,olfactory sensitivity was decreased in diabetic rats.Meanwhile,the number of Brd U-positive and Brd U+/DCX+double-labeled cells was lower in the subventricular zone of diabetic rats compared with agematched normal rats.Western blot results revealed downregulated expression of insulin receptorβ,phosphorylated glycogen synthase kinase 3β,and β-catenin in the subventricular zone of diabetic rats.Altogether,these results indicate that diabetes mellitus causes insulin deficiency,which negatively regulates glycogen synthase kinase 3β and enhances β-catenin degradation,with these changes inhibiting neural stem cell proliferation.Further,these signaling pathways affect proliferation and differentiation of neural stem cells in the subventricular zone.Dysfunction of subventricular zone neural stem cells causes a decline in olfactory bulb structural plasticity and impairs olfactory sensitivity in diabetic rats.