Neurogenesis dynamics in the olfactory bulb:deciphering circuitry organization, function, and adaptive plasticity

Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased complexity and restructuring of neural network structures, as well as the addition of new granule granule cells that aid in olfactory adaptation. Additionally, the manuscript underscores the importance of employing precise methodologies to elucidate the specific roles of adult neurogenesis amidst conflicting data and varying experimental paradigms. Understanding these processes is essential for gaining insights into the complexities of olfactory function and behavior.

Olfactory dysfunction and its related molecular mechanisms in Parkinson’s disease

Changes in olfactory function are considered to be early biomarkers of Parkinson’s disease.Olfactory dysfunction is one of the earliest non-motor features of Parkinson’s disease,appearing in about 90%of patients with early-stage Parkinson’s disease,and can often predate the diagnosis by years.Therefore,olfactory dysfunction should be considered a reliable marker of the disease.However,the mechanisms responsible for olfactory dysfunction are currently unknown.In this article,we clearly explain the pathology and medical definition of olfactory function as a biomarker for early-stage Parkinson’s disease.On the basis of the findings of clinical olfactory function tests and animal model experiments as well as neurotransmitter expression levels,we further characterize the relationship between olfactory dysfunction and neurodegenerative diseases as well as the molecular mechanisms underlying olfactory dysfunction in the pathology of early-stage Parkinson’s disease.The findings highlighted in this review suggest that olfactory dysfunction is an important biomarker for preclinical-stage Parkinson’s disease.Therefore,therapeutic drugs targeting non-motor symptoms such as olfactory dysfunction in the early stage of Parkinson’s disease may prevent or delay dopaminergic neurodegeneration and reduce motor symptoms,highlighting the potential of identifying effective targets for treating Parkinson’s disease by inhibiting the deterioration of olfactory dysfunction.

Progress in Research on Insect Olfactory Perception of Habitat Odor Molecules

A highly sensitive olfactory system allows insects to precisely identify and position volatile compounds from different sources in their habitats,and plays a crucial role in their foraging,mating,and oviposition activities.During evolution,insects have successfully developed a large and complex olfactory system to adapt to heterogeneous environments,enabling the maintenance of inset population.A comprehensive examination of the olfactory system of insects may therefore yield novel insights into the development of innovative pest control and prevention strategies,as well as the study of olfactory mechanisms in vertebrates and even humans.This paper outlines the current state of research into the signal transduction mechanism by which insects perceive the olfactory molecules of their habitats.The aim of this review is to provide a reference point for future studies into the olfactory perception mechanism and its potential applications in pest management.

Acupuncture for olfactory dysfunction in infected COVID-19 patients:Study protocol for a randomized,sham-controlled clinical trial

Background:Olfactory dysfunction(OD)is a common symptom of Corona Virus Disease 2019(COVID-19).It is defined as the reduced or distorted ability to smell during sniffing(orthonasal olfaction)and represents one of the early symptoms in the clinical course of COVID-19 infection.A large online questionnaire-based survey has shown that some post-COVID-19 patients had no improvement 1 month after discharge from the hospital.Objective:To explore the efficacy of acupuncture for OD in COVID-19 infected patients and to determine whether acupuncture could have benefits over sham acupuncture for OD in post-COVID-19 patients.Methods:This is a single-blind,randomized controlled,cross-over trial.We plan to recruit 40 post-COVID-19 patients with smell loss or smell distortions lasting for more than 1 month.Qualified patients will be randomly allocated to the intervention group(real acupuncture)or the control group(sham acupuncture)at a 1:1 ratio.Each patient will receive 8 sessions of treatment over 4 weeks(Cycle 1)and a 2-week follow-up.After the follow-up,the control group will be subjected to real acupuncture for another 4 weeks(Cycle 2),and the real acupuncture group will undergo the 4-week sham acupuncture.The primary outcomes will be the score changes on the questionnaire of olfactory functioning and olfaction-related quality of life at week 6,8,12,and 14 from the baseline.The secondary outcomes will be the changes in the olfactory test score at week 6 and 12 from the baseline measured by using the Traditional Chinese version of the University of Pennsylvania Smell Identification Test(UPSIT-TC).Discussion:The results of this trial will help to determine the effectiveness of acupuncture for OD in post-COVID-19 patients.This may provide a new treatment option for patients.

Prospects for the use of olfactory mucosa cells in bioprinting for the treatment of spinal cord injuries

The review focuses on the most important areas of cell therapy for spinal cord injuries.Olfactory mucosa cells are promising for transplantation.Obtaining these cells is safe for patients.The use of olfactory mucosa cells is effective in restoring motor function due to the remyelination and regeneration of axons after spinal cord injuries.These cells express neurotrophic factors that play an important role in the functional recovery of nerve tissue after spinal cord injuries.In addition,it is possible to increase the content of neurotrophic factors,at the site of injury,exogenously by the direct injection of neurotrophic factors or their delivery using gene therapy.The advantages of olfactory mucosa cells,in combination with neurotrophic factors,open up wide possibilities for their application in threedimensional and four-dimensional bioprinting technology treating spinal cord injuries.

Post-COVID-19 persistent olfactory,gustatory,and trigeminal chemosensory disorders:Definitions,mechanisms,and potential treatments

The nose and the oral cavities are the main sites for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry into the body.Smell and taste deficits are the most common acute viral manifestations.Persistent smell disorders are the most common and bothersome complications after SARS-CoV-2 infection,lasting for months to years.The mechanisms and treatment of persistent post-coronavirus disease 2019(COVID-19)smell and taste disorders are still challenges.Information sources for the review are PubMed,Centers for Disease Control and Prevention,Ovid Medline,Embase,Scopus,Web of Science,International Prospective Register of Systematic Reviews,Cumulative Index to Nursing and Allied Health Literature,Elton Bryson Stephens Company,Cochrane Effective Practice and Organization of Care,Cooperation in Science and Technology,International Clinical Trials Registry Platform,World Health Organization,Randomized Controlled Trial Number Registry,and MediFind.This review summarizes the up-to-date information about the prevalence,patterns at onset,and prognoses of post-COVID-19 smell and taste disorders,evidence for the neurotropism of SARS-CoV-2 and the overlap between SARSCoV-1,Middle East respiratory syndrome coronavirus,and SARS-CoV-2 in structure,molecular biology,mode of replication,and host pathogenicity,the suggested cellular and molecular mechanisms for these post-COVID19 chemosensory disorders,and the applied pharmacotherapies and interventions as trials to treat these disorders,and the recommendations for future research to improve understanding of predictors and mechanisms of these disorders.These are crucial for hopeful proper treatment strategies.

Gene and protein expression profiles of olfactory ensheathing cells from olfactory bulb versus olfactory mucosa

Olfactory ensheathing cells(OECs) from the olfactory bulb(OB) and the olfactory mucosa(OM) have the capacity to repair nerve injury. However, the difference in the therapeutic effect between OB-derived OECs and OM-derived OECs remains unclear. In this study, we extracted OECs from OB and OM and compared the gene and protein expression profiles of the cells using transcriptomics and non-quantitative proteomics techniques. The results revealed that both OB-derived OECs and OM-derived OECs highly expressed genes and proteins that regulate cell growth, proliferation, apoptosis and vascular endothelial cell regeneration. The differentially expressed genes and proteins of OB-derived OECs play a key role in regulation of nerve regeneration and axon regeneration and extension, transmission of nerve impulses and response to axon injury. The differentially expressed genes and proteins of OM-derived OECs mainly participate in the positive regulation of inflammatory response, defense response, cytokine binding, cell migration and wound healing. These findings suggest that differentially expressed genes and proteins may explain why OB-derived OECs and OM-derived OECs exhibit different therapeutic roles. This study was approved by the Animal Ethics Committee of the General Hospital of Ningxia Medical University(approval No. 2017-073) on February 13, 2017.

Olfactory ensheathing cell transplantation improves sympathetic skin responses in chronic spinal cord injury

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.

Simplified methods to isolate,culture and purify olfactory ensheathing cells

Conventional methods for harvesting, culturing and purifying olfactory ensheathing cells are complicated, time-consuming, and poorly reproducible. Olfactory bulbs were detached from adult Sprague Dawley rats and olfactory ensheathing cells were isolated using shearing, dispersion processes. After the primary cultures reached confluence, the cells were purified using a three-step process. The olfactory ensheathing cells attached and grew rapidly. The purity of the olfactory ensheathing cells increased following the three purification steps, eventually exceeding 95%. These cells could be maintained for an extended period time in culture. This simple, inexpensive, reproducible method of harvesting, culturing and purifying olfactory ensheathing cells shortens the culture cycle and provides sufficient olfactory ensheathing cells of controllable purity.

Nogo-A expression in injured spinal cord following human olfactory mucosa-derived olfactory ensheathing cells transplantation

Transplantation of olfactory bulb-derived olfactory ensheathing cells （OECs） promotes motor functional recovery in rats with acute spinal cord injury, possibly by Nogo-A expression changes at the injury site. The present study transplanted OECs derived from the olfactory mucosa （OM） of rats OM-derived OEC （OM-OEC） transplantation significantly reduced the increase of Nogo-A protein and mRNA expression caused by spinal cord injury, supporting the hypothesis that OM-OECs improve spinal cord regeneration by reducing Nogo-A expression.

Isolation,culture,and purification of olfactory mucosa-derived olfactory ensheathing cells using modified differential attachment with low concentration serum

BACKGROUND：Studies have demonstrated that olfactory mucosa can promote the regeneration and formation of axonal medullary sheath of injured neurons. To date, olfactory ensheathing cells （OECs） utilized in basic and clinical research arise primarily from the olfactory bulb mucosa. However, little is known regarding culture, purification, and biological properties of OECs . OBJECTIVE： To isolate and culture OECs utilized modified, differential attachment in combination with neurotrophic factor 3 （NT3） and low concentration serum to explore an optimal in vitro culture method for OECs.DESIGN, TIME AND SETTING： Single-sample observation was performed at the Medical Experimental Center of Stomatology College, Xi＇an Jiaotong University between March 2006 and December 2007. MATERIALS： Twelve samples from aborted embryos, 4-6 months, were used to isolate OECs; rabbit-anti-human p75NTR and glial fibrillary acidic protein （GFAP） antibody were provided by Sigma, USA. METHODS： The differential time was six hours. This was repeated twice, based on Nash＇s differential attachment. Attached OECs were cultured in DMEM-F12 culture medium containing 10% fetal bovine serum （FBS） or 2.5% FBS and NT3. MAIN OUTCOME MEASURES： OEC morphology was observed, and p75NTR and GFAP immunocyto-chemistry was used for identification and purity detection. RESULTS： Some cells attached after three days in culture. Several cells possessed short neurites with good refractivity. Some shuttle-shaped fibroblasts could be seen. On day six, more cells attached, exhibiting a three-dimensional appearance. Many cells appeared dipolar or tripolar, with slender neurites, and fibroblasts were clustered. On day nine, the number of dipolar or tripolar cell bodies with slender neurites was increased, and fibroblasts were clustered. On day 15, fibroblasts occupied the majority of the bottom of the culture bottle, with several OECs surviving at the upper layer. OECs were positive for P75NTR and GFAP expression, as identified by an immunocytologically stained brown cell body and neurites. However, fibroblasts were P75NTR and GFAP-negative. On day 9, OEC purity reached 81%, and the number of proliferating fibroblasts significantly increased. By the end of day 12, OEC purity was reduced to 56%. CONCLUSION： Modified differential attachment, in combination with low concentration serum and NT3, removes fibroblasts and reduces OEC loss. This is an appropriate method for the isolation and culture of human fetal olfactory mucosa-derived OECs.

Combined Transplantation of Neural Stem Cells and Olfactory Ensheathing Cells Improves the Motor Function of Rats with Intracerebral Hemorrhage

Objective To investigate the effects of combined transplantation of neural stem cells （NSC） and olfactory ensheathing cells （OEC） on the motor function of rats with intracerebral hemorrhage. Methods In three days after a rat model of caudate nucleus hemorrhage was established, NSCs and OEC, NSC, OEC （from embryos of Wistar rats） or normal saline were injected into bematomas of rats in combined transplantation group, NSC group, OEC group, and control group, respectively. Damage of neural function was scored before and in 3, 7, 14, 30 days after operation. Tissue after transplantation was observed by immunocytochemistry staining. Results The scores for the NSC, OEC and co-transplantation groups were significantly lower in 14 and 30 days after operation than in 3 days after operation （P〈0.05）. The scores for the NSC and OEC groups were significantly lower than those for the control group only in 30 days after operation （P〈0.05）, while the difference for the NSC-OEC group was significant in 14 days after operation （P〈0.05）. Immunocytochemistry staining revealed that the transplanted OEC and NSC could survive, migrate and differentiate into neurons, astrocytes, and oligodendrocytes. The number of neural precursor cells was greater in the NSC and combined transplantation groups than in the control group. The number of neurons differentiated from NSC was significantly greater in the co-transplantation group than in the NSC group. Conclusion Co-transplantation of NSC and OEC can promote the repair of injured tissue and improve the motor fimction of rats with intracerebral hemorrhage.

Effects of total saponins of Panax notoginseng on immature neuroblasts in the adult olfactory bulb following global cerebral ischemia/reperfusion

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.

Hyperhomocysteinemia induces injury in olfactory bulb neurons by downregulating Hes1 and Hes5 expression

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.

Olfactory ensheathing cell transplantation in 106 patients with old spinal cord injury Differences in ages,sexes,disease courses,injured types and sites

BACKGROUND： It has been demonstrated that the transplantation of olfactory ensheathing cell （OEC） can promote the recovery of neurological function through ameliorating the local internal environment in spinal cord injury. OBJECTIVE： To evaluate the recent efficacy of OEC transplantation on old spinal cord injury. DESIGN： A self-controlled experiment. SETTING： Department ofNeurosurgery, Taian Rongjun Hospital of Shandong Province. PARTICIPANTS： Totally 106 inpatients with old spinal cord injury were selected from the Department of Neurosurgery, Taian Rongjun Hospital of Shandong Province from June 2004 to December 2006, including 97 males and 9 females. Inclusive criteria： ① Complete data; ② Informed with the fact; ③No further recover neurological function after drug therapy （neurotrophic factor, GM-1）, traditional Chinese medicine, physiotherapy and rehabilitative exercises; ④ No obvious compression of the injured spinal cord displayed by MRI examination. METHODS： ① The olfactory bulb was obtained from embryo of induced labor in middle pregnancy above 4 months supplied voluntarily by pregnant women, and the survived cells after purification and culture for 1 - 2 weeks were collected. Dura mater was incised by posterior approach, then the cultured OEC suspension was transplanted to corresponding regions by means of multi-target injection using microscope. ② The patients were evaluated for twice with the standards suggested by American Spinal Injury Association （ASIA） at admission and 2 - 4 weeks postoperatively, in order to investigate the efficacy in different age groups, different sites and at different time points after the OEC transplantation. ③ Standards for evaluation： The International Standard for Neurological and Functional Classification of Spinal Cord Injury set by ASIA： The highest score of motor function was 100 points; The highest score of sensory function was 112 points for light touch and 112 for acupuncture sense. Frankel grading modified by ASIA in 1992： grades A, B, C, D and E （grade A for complete injury, and grade E for normal）. ④ The data were statistically processed by Professor Cheng from the Department of Statistics, Taishan Medical College. MAIN OUTCOME MEASURES： Changes of motor and sensory functions postoperatively. RESULTS： All the 106 patients with old spinal cord injury were involved in the analysis of results. Grade A （n =72） at admission recovered to grade B in 31 cases and grade C in 7 cases after operation; Grade B （n =9） recovered to grade C in 2 cases; Grade C （n =15） recovered to grade D in 4 cases; Grade D （n =10） recovered to grade E in 1 cases, which referred to normal sensory and motor functions. The scores of motor, tactile sensation and pain sensation postoperatively were all obviously higher than those at admission （t =5.381, 7.036, 7.775, P 〈 0.05）. The recovery of motor function had obvious difference among patients of different ages （F =5.235, P =0.001）. There were no obvious differences in the recovery of motor and sensory functions among patients of different sexes, courses, injured types and sites. CONCLUSION： The neurological function can be ameliorated in a short time after OEC transplantation in patients with old spinal cord injury. The efficacy is generally the same in patients of different sexes, courses, injured types and sites, but there are differences in the effects on motor function of patients of different ages.

Meta analysis of olfactory ensheathing cell transplantation promoting functional recovery of motor nerves in rats with complete spinal cord transection

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.

Spontaneous firing in olfactory bulb neurons of Bufo bufo gargarizans in and after hibernation

Microelectrode technique was used to record the spontaneous electrical activities of the neurons in olfactory bulb of the Bufo bufo gargarizans, both in hibernation and after hibemation. This study investigated the electrophysiological characteristics of amphibian olfactory bulb in the period of hibernation and after hibernation and its effects on the start of hibernation and spontaneous awakening. The research showed four forms of spontaneous firings： single spontaneous firing, burst spontaneous firing, irregular spontaneous firing and consecutive single spontaneous firing. The single spontaneous firing includes slow depolarized spontaneous firing and fast depolarized spontaneous firing, and the slow depolarized spontaneous firing occurs only during the hibernation period. In hibernation, the low amplitude and low frequency firing with a longer duration may be relevant to maintaining the tonicity of the central nervous system in toads that are in hibernation, and this kind of firing may also provide an excited basis for their arousal from hibernation. After hibernation, the amplitude and frequency of firing increase, but the firing duration gets shorter. This form of short-term firing, which may be a phenomenon of sensory neurons fast adapting, is one of the neuronal mechanisms for the arousal of hibernating animals.

Transplantation of low-power laser-irradiated olfactory ensheathing cells to promote repair of spinal cord injury in rats

BACKGROUND： Previous studies have demonstrated that low-power laser （LPL） irradiation can promote the regeneration of peripheral nerves and central nerves, as well as influence cellular proliferation. Therefore, it is thought to be a potential treatment for spinal cord injury. OBJECTIVE： Utilizing histological observations and behavioral evaluations, the aim of this study was to investigate the influence of transplanted olfactory ensheathing cells （OECs）, irradiated by LPL, on functional repair of rats following transversal spinal cord injury. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the animal experimental center in the First Affiliated Hospital of Xinjiang Medical University between January 2007 and February 2008. MATERIALS： A total of 52 Sprague Dawley rats were included in this experiment. Twelve rats were used to harvest OECs, some of which were irradiated by LPL on days 3, 5, and 7 in culture. The remaining 40 rats were used to establish T12 complete spinal cord transection injury. DMEM/F12 medium was purchased from Sigma, USA, Fluorogold was provided by Chemicon, USA, and the LY/JG650-D500-16 low-power laser was produced by Xi＇an Lingyue Electromechanical Science And Technology Co., Ltd., China. METHODS： The successful rat models were randomly divided into three groups： OEC transplantation, LPL-irradiated OEC transplantation, and control. These animals were microinjected with OEC suspension, LPL-irradiated OEC suspension, and DMEM/F12 medium （10μL） respectively 4 weeks after spinal cord was completely transected at the T12 level. MAIN OUTCOME MEASURES： Spinal cord injury was observed using hematoxylin-eosin staining Expression of nerve growth factor receptor p75 and glial fibrillary acidic protein were determined using immunohistochemical staining. Regeneration of spinal nerve fibers in rats was assayed by Fluorogold retrograde labeling method. Basso, Beattie and Bresnahan （BBB） scores were used to evaluate motor functions of rat lower limbs. RESULTS： Structural disturbances were observed following spinal cord injury in each group, and a large amount of scar tissue covered the broken ends, accompanied by porosis and inflammatory cell infiltration. Following OEC transplantation, the distal end connected to the proximal end. nerve growth factor receptor p75 and glial fibrillary acidic protein immunohistochemistry revealed positive OECs in the cephalad and caudal area of rats that received LPL-irradiated OEC transplantation. In the OECs group, only glial fibrillary acidic protein staining was observed. No staining was found in the control group. Neural fibers labeled with Fluorogold extended across the lesion area and into the cephalad and caudal area in the OECs and LPL-irradiated OECs groups, but were not present in the control group. BBB scores revealed statistically significant differences among the three groups （P 〈 0.05）： OECs irradiated by LPL group 〉 OECs group 〉 control group. CONCLUSION： Transplantation of OECs and LPL-irradiated OECs promoted functional repair in the injured spinal cord of rats, although LPL-irradiated OECs resulted in greater beneficial effects.

Differentiation of human olfactory mucosa mesenchymal stem cells into photoreceptor cells in vitro

AIM：To investigate whether the human olfactory mucosa mesenchymal stem cells（OM-MSCs）can differentiate into photoreceptor cells in vitro.METHODS：Through the olfactory mucosa adherent method,olfactory mucosa was isolated,cultured and identified in vitro among mesenchymal stem cells.The cell surface markers were analyzed by flow cytometry,induced to differentiate into retinal photoreceptor cells in vitro,and the expression of rhodopsin was observed and identified by Immunofluorescence and Western blot methods.RESULTS：OM-MSCs from human were spindle cellbased,and showing radial colony arrangement.OM-MSCs were negative for CD34,CD45 and CD105,but positive for CD73 and CD90.Following induction,a strong positive reaction was produced by photoreceptor specific marker rhodopsin in the cells.CONSLUSION：This novel finding demonstrates that OM-MSCs can be cultured and expanded in vitro.They possess biological characteristics of mesenchymal stem cells,and have the ability to be induced into retinal cells.

Olfactory ensheathing cell transplantation and inhibition of NogoA,NgR and RhoA expression in the damaged zone to ameliorate spinal cord injury

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.