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The present study aimed to investigate the associations of tumor inhibitor of growth 4 (ING4) with tumor cell proliferation and microvessel density (MVD) in human glioma. Semi-quantitative reverse transcription polymerase chain reaction, western blotting and immunohistochemistry (IHC) were used to detect the level of ING4 expression in normal brain tissues and glioma tissues of different pathological grades. The cell proliferation index (PI) and the level of MVD were detected using IHC, facilitating the analysis of the correlation between ING4 and cellular proliferation and MVD in human glioma. The expression levels of ING4 mRNA and protein were significantly lower in the glioma tissues compared with the normal brain tissues (P<0.05) and decreased as the pathological grade of the glioma tissue increased (P<0.05). PI was reduced in the ING4 protein positively expressed (ING4+) glioma tissues compared with the ING4 protein negatively expressed (ING4-) glioma tissues (P≤0.01). The level of MVD was significantly higher in the glioma tissues than that in the normal brain tissues (P≤0.01), while the level of MVD decreased in the ING4+ glioma tissue compared with the ING4- glioma tissue (P≤0.001). A Spearman's rank correlation test revealed that ING4 protein expression was negatively correlated with PI and MVD. ING4 might inhibit tumor proliferation and angiogenesis in human glioma. The expression of ING4 was also associated with the pathological grading of the glioma tissue and negatively correlated with cellular proliferation and MVD in human glioma.
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PURPOSE: Achieving a radiographic gross total resection in high-grade gliomas improves overall survival. Many technologies such as intraoperative microscope, intraoperative ultrasound, fluorescence imaging, and intraoperative magnetic resonance imaging have been applied to improve tumor resection. However, most commercial available magnetic resonance imaging contrast agents have limited permeability across the blood-brain barrier and are cleared rapidly from circulation. Fluorescence imaging discriminates tumor from normal tissue and provides a promising new strategy to maximize sage surgical resection of tumor. However, the penetration depth of fluorescence imaging is generally low. MATERIALS AND METHODS: In this study, a new type of magnetite NaGdF4:Yb(3+),Er(3+),Li(+)@NaGdF4 (UCNPs) core-shell nanoparticles, coated with SiO2 and further functionalized with glioma and blood-brain barrier targeting motifs, was prepared for dual-modal in vivo upconversion imaging and magnetic resonance imaging. RESULTS: The as-prepared multifunctional upconversion nanoparticles (UCNPs@SiO2-CX-Lf) were biocompatible, showed strong upconversion luminescence under excitation of 980 nm, and provided high signal-to-noise ratio in vivo. Moreover, UCNPs@SiO2-CX-Lf nanoparticles showed a high relaxivity of 1.25 S(-1 )mM(-1) and were successfully applied as contrast agent for magnetic resonance imaging in tumor xenograft rat model with prolonged tumor signal enhancement. In vivo and magnetic resonance imaging Upconversion Luminescence (UCL) imaging results indicated that these particles can across the blood-brain barrier, bind to glioma, gave bright UCL signal and T1 magnetic resonance imaging contrast. CONCLUSIONS: Targeted UCL and magnetic resonance imaging dual-modal in vivo imaging using Yb(3+)/Er(3+)/Li(+) codoped NaGdF4 core-shell nanostructure can serve as a platform technology for the next generation of intraoperative probes for image-guided tumor resection.
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Neoplasias Encefálicas/patologia , Óxido Ferroso-Férrico/química , Glioma/patologia , Medições Luminescentes/métodos , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Animais , Neoplasias Encefálicas/diagnóstico por imagem , Linhagem Celular Tumoral , Meios de Contraste/síntese química , Glioma/diagnóstico por imagem , Humanos , Aumento da Imagem/métodos , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Emerging evidence has shown that microRNAs (miRNAs) participate in human carcinogenesis as tumor suppressors or oncogenes. It has been suggested that four common single nucleotide polymorphisms (SNPs; miR-146aG > C, 149C > T, 196a2C > T, and 499A > G) are associated with susceptibility to numerous malignancies. However, published results are inconsistent and inclusive. To further investigate the role of these loci, we examined the association of the miRNA polymorphisms with the risk of gliomas in a Han population in northeastern China. Both miR-146aG > C and 196a2C > T showed allelic differences between glioma patients and healthy controls in the studied population, with an OR of 1.30 (P = 0.0006) and an odds ratio (OR) of 1.25 (P = 0.003), respectively. Logistic regression analysis also revealed that the 146aG > C and 196a2C > T wild-type homozygous carriers had an increased glioma risk compared to the variant carriers. Besides, in pairwise comparisons two SNP combinations were associated with the risk of glioma. Among others, carriers of both homozygous risk genotypes, i.e., 146aGG and 196a2CC were associated with a nearly 4-fold increased risk of glioma (OR = 3.77, P = 1.3 × 10(-4)). Overall, glioma risk increased with increasing numbers of risk variant alleles. These results suggest that the miR-146aG > C and 196a2C > T might influence the risk of developing glioma in a northeastern Han Chinese population.
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Neoplasias Encefálicas/genética , Predisposição Genética para Doença , Glioma/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Estudos de Casos e Controles , China , Feminino , Homozigoto , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Hyperpneumatization of the temporal bone with extension into the occipital bone and even the parietal bones is a rare condition. We report a case in which the patient suffered periodically from a palpable mass in the parietal-occipital region which originated from extensive occipital bone pneumatization. Computed tomography examination revealed extensive temporal and occipital pneumatization and subperiosteal pneumatoceles, which was corrected by surgery.
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Doenças Ósseas/diagnóstico por imagem , Enfisema/diagnóstico por imagem , Osso Occipital/diagnóstico por imagem , Pneumocefalia/diagnóstico por imagem , Osso Temporal/diagnóstico por imagem , Adulto , Doenças Ósseas/complicações , Doenças Ósseas/cirurgia , Diagnóstico Diferencial , Enfisema/etiologia , Enfisema/cirurgia , Humanos , Masculino , Osso Occipital/cirurgia , Periósteo/diagnóstico por imagem , Periósteo/cirurgia , Pneumocefalia/complicações , Pneumocefalia/cirurgia , Radiografia , Osso Temporal/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Research into retinal ganglion cell (RGC) degeneration and neuroprotection after optic nerve injury has received considerable attention and the establishment of simple and effective animal models is of critical importance for future progress. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, the optic nerves of Wistar rats were semi-transected selectively with a novel optic nerve quantitative amputator. The variation in RGC density was observed with retro-labeled fluorogold at different time points after nerve injury. The densities of surviving RGCs in the experimental eyes at different time points were 1113.69±188.83 RGC/mm² (the survival rate was 63.81% compared with the contralateral eye of the same animal) 1 week post surgery; 748.22±134.75/mm² (46.16% survival rate) 2 weeks post surgery; 505.03±118.67/mm² (30.52% survival rate) 4 weeks post surgery; 436.86±76.36/mm² (24.01% survival rate) 8 weeks post surgery; and 378.20±66.74/mm² (20.30% survival rate) 12 weeks post surgery. Simultaneously, we also measured the axonal distribution of optic nerve fibers; the latency and amplitude of pattern visual evoke potentials (P-VEP); and the variation in pupil diameter response to pupillary light reflex. All of these observations and profiles were consistent with post injury variation characteristics of the optic nerve. These results indicate that we effectively simulated the pathological process of primary and secondary injury after optic nerve injury. CONCLUSIONS/SIGNIFICANCE: The present quantitative transection optic nerve injury model has increased reproducibility, effectiveness and uniformity. This model is an ideal animal model to provide a foundation for researching new treatments for nerve repair after optic nerve and/or central nerve injury.
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Sobrevivência Celular/fisiologia , Modelos Animais de Doenças , Procedimentos Neurocirúrgicos/instrumentação , Procedimentos Neurocirúrgicos/métodos , Traumatismos do Nervo Óptico/cirurgia , Células Ganglionares da Retina/fisiologia , Animais , Contagem de Células , Potenciais Evocados Visuais/fisiologia , Imuno-Histoquímica , Traumatismos do Nervo Óptico/patologia , Ratos , Ratos Wistar , Reflexo Pupilar/fisiologiaRESUMO
OBJECTIVE: We aimed to investigate whether an innovative growth factor-laden scaffold composed of acellular sciatic nerve (ASN) and brain-derived neurotrophic factor (BDNF) could promote axonal regeneration and functional recovery after spinal cord injury (SCI). METHODS: Following complete transection at the thoracic level (T9), we immediately transplanted the grafts between the stumps of the severed spinal cords. We evaluated the functional recovery of the hindlimbs of the operated rats using the BBB locomotor rating scale system every week. Eight weeks after surgery, axonal regeneration was examined using the fluorogold (FG) retrograde tracing method. Electrophysiological analysis was carried out to evaluate the improvement in the neuronal circuits. Immunohistochemistry was employed to identify local injuries and recovery. RESULTS: The results of the Basso-Beattie-Bresnahan (BBB) scale indicated that there was no significant difference between the individual groups. The FG retrograde tracing and electrophysiological analyses indicated that the transplantation of ASN-BDNF provided a permissive environment to support neuron regeneration. CONCLUSION: The ASN-BDNF transplantation provided a promising therapeutic approach to promote axonal regeneration and recovery after SCI, and can be used as part of a combinatory treatment strategy for SCI management.
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Fator Neurotrófico Derivado do Encéfalo/metabolismo , Nervo Isquiático/fisiopatologia , Traumatismos da Medula Espinal/terapia , Animais , Axônios/patologia , Membrana Basal/patologia , Barreira Hematoencefálica , Eletrofisiologia/métodos , Feminino , Microscopia Eletrônica de Varredura/métodos , Microscopia Eletrônica de Transmissão/métodos , Regeneração Nervosa , Neurônios/metabolismo , Ratos , Nervo Isquiático/ultraestrutura , Medula Espinal/patologia , Transplante HomólogoRESUMO
OBJECTIVE: To clarify the oriented classification, relationships, and variations of the abducens nerve and provide a detailed description of its microsurgical anatomic features. METHODS: A microsurgical anatomic dissection of the abducens nerve was performed in 100 specimens obtained from 50 adult cadaveric heads fixed in formalin and two adult cadaveric heads stained with hematoxylin and eosin for histological examination. Important neurovascular and structural relationships of the abducens nerve were observed. RESULTS: The abducens nerve was divided into five segments (cisternal, petroclival, internal carotid artery, fissural, and intraconal). It coursed in the petroclival venous confluence and there was a complex anatomic relationship. Two new types of abducens nerve variations were found. In one type, the duplicated nerve is split into two branches for a limited length in the cavernous sinus (CS). The other is a complex type, which has a complex course and pattern. This type of duplicated abducens nerve has a communicating branch in the cistern and numerous fasciculi in the CS. In addition, the two branches do not accompany each other for the entire course in the CS. CONCLUSION: The vulnerability of the abducens nerve results from diverse factors. The inferolateral trunk, which arises from the intracavernous segment of carotid artery (also called the artery of the inferior CS), is an important landmark for finding the abducens nerve and sympathetic nerve. Variations of the abducens nerve are not rare. Keeping variations of the nerve in mind is important during skull base operations and transvenous endovascular interventions. Understanding the relationship of the abducens nerve with adjacent structures will help us in preparing for safe surgery.
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Nervo Abducente/anatomia & histologia , Aneurisma Intracraniano/cirurgia , Microcirurgia/métodos , Nervo Abducente/cirurgia , Adulto , Artéria Cerebral Anterior/anatomia & histologia , Artéria Cerebral Anterior/cirurgia , Cadáver , Artéria Carótida Interna/anatomia & histologia , Artéria Carótida Interna/cirurgia , Dissecação , Feminino , Humanos , Masculino , Estudos de Amostragem , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To study the related factors of early post-operative prognosis of meningiomas. METHODS: The clinical data of 953 patients with meningiomas were recorded and statistically analyzed with χ(2) test of single factor and logistic regression model of multivariate factors. Patient age; tumor size; tumor location; pre-operative complication of patients such as hypertension, diabetes, heart disease and cerebral infarction; the extent of tumor resection; hemorrhagic shock; blood loss or hemorrhagic shock and brain swelling intra-operatively were taken as variables. The prognosis was evaluated by postoperative Karnofsky performance scale. RESULTS: The prognosis was significantly correlated with the patient age, tumor size, tumor location, preoperative cerebral infarction, the extent of tumor resection, blood loss and hemorrhagic shock intra-operatively (P < 0.05). Such factors as tumor size, preoperative cerebral infarction, the extent of tumor resection (Simpson's scale) and intra-operative hemorrhagic shock were independent risk factors of prognosis for meningiomas. Other factors, such as hypertension, diabetes and heart disease, were unrelated with the prognosis of meningiomas (P > 0.05). CONCLUSION: Patient age, tumor location and pre-operative complications of patients maybe affect the early postoperative prognosis of meningiomas. But such factors as tumor size, preoperative cerebral infarction, the extent of tumor resection and intra-operative hemorrhagic shock are independent risk factors for the post-operative prognosis of meningiomas.
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Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Humanos , Lactente , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/cirurgia , Meningioma/patologia , Meningioma/cirurgia , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
Bifunctional nanoprobes with both magnetic and optical contrast have been developed for ultra-sensitive brain tumor imaging at the cellular level. The nanoprobes were synthesized by simultaneously incorporating a magnetite nanoparticle cluster and fluorescence dyes into silica encapsulation by a sol-gel approach under ultrasonic treatment. The nanoprobes maintain superparamagnetic behavior at room temperature and possess enhanced transverse relaxivity and good photostability. As a glioma targeting ligand, chlorotoxin was covalently bonded to the surface of the nanoprobes. In vitro cellular uptake assays demonstrated that the nanoprobes were highly specific, taken up by human U251-MG glioma cells via receptor-mediated endocytosis. The labeled glioma cells were readily detectable by both MR imager and confocal laser scanning microscopy.
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Neoplasias Encefálicas/diagnóstico , Óxido Ferroso-Férrico/química , Corantes Fluorescentes/química , Glioma/diagnóstico , Imageamento por Ressonância Magnética/métodos , Venenos de Escorpião , Dióxido de Silício/química , Linhagem Celular Tumoral , Humanos , Venenos de Escorpião/químicaRESUMO
UNLABELLED: OBJECTIVE; To investigate a new composite matrix (BMSCs seeded on the denuded human amniotic membrane, BMSCs-DHAM) bridging the both stumps of spinal cord injury in rats to promote axon regeneration and improve motor function of hind limbs. METHODS: The human amniotic membrane (HAM) was voluntarily donated by the healthy pregnant women after a caesarean section. The cells on the HAM were completely removed with a tryptic and mechanical approach to prepare DHAM. The BMSCs were separated and cultured from 4-week-old female rats (n = 4), then the forth passage of BMSCs were labeled by PKH26 and seeded on DHAM (BMSCs-DHAM). The growing state of BMSCs was observed under the microscopy. Moreover, 40 female rats (8-week-old, weighting 200-220 g) were made spinal cord injury models by transecting at T9 level, and were randomly divided into 4 groups (each group, n = 10). The both stumps were respectively wrapped by BMSCs-DHAM or simple DHAM in groups A and C, and the same dose of BMSCs or physiological saline were also respectively injected the central lesion in groups B and D. At 12 weeks after surgery, the functional recovery of the hindlimbs was evaluated by the BBB locomotor rating score, and other indexes were tested including cortical motion evoked potential (MEP), anterograde biotinylated dextran amine (BDA) tracing, and immunofluorescence of neurofilament protein 200 (NF-200). RESULTS: HE staining proved that the DHAM was devoid of cellular components by this way, and BMSCs grew well on the substrate under the microscopy. At 12 weeks after operation, the BBB score (12.50 +/- 1.26) in group A was significantly higher than those of other groups (P < 0.05), and the recovery in latency (3.52 +/- 2.45) ms and amplitude (480.68 +/- 18.41) microV of MEP was also obviously improved in group A (P < 0.05) when compared with other groups. In addition, anterograde BDA tracing revealed that the rate of the positive BDA axons 54.12% +/- 3.30% under the lesion level in group A was higher than those of other groups (P < 0.05), and lots of the regeneration axons (positive NF-200) were found to grow into the spinal cord under the composite matrix in group A. CONCLUSION: The BMSCs-DHAM composite matrix can improve hindlimb motor function to some extent after spinal cord injury. It will be widely applied as the matrix material in the future.
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Transplante de Células-Tronco Mesenquimais , Regeneração Nervosa , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/terapia , Engenharia Tecidual/métodos , Âmnio/citologia , Animais , Células Cultivadas , Feminino , Humanos , Atividade Motora , Plasticidade Neuronal , Ratos , Ratos WistarRESUMO
AIM: To determine whether glioma cells can be specifically and efficiently targeted by superparamagnetic iron oxide nanoparticle (SPIO)-fluorescein isothiocyanate (FITC)-chlorotoxin (SPIOFC) that is detectable by magnetic resonance imaging (MRI) and optical imaging. METHODS: SPIOFC was synthesized by conjugating SPIO with FITC and chlorotoxin. Glioma cells (human U251-MG and rat C6) were cultured with SPIOFC and SPIOF (SPIO-FITC), respectively. Neural cells were treated with SPIOFC as the control for SPIOFC-targeted glioma cells. The internalization of SPIOFC by glioma cells was assessed by MRI and was quantified using inductively-coupled plasma emission spectroscopy. The optical imaging ability of SPIOFC was evaluated by confocal laser scanning microscopy. RESULTS: Iron per cell of U251 (72.5+/-1.8 pg) and C6 (74.9+/-2.2 pg) cells cultured with SPIOFC were significantly more than those of U251 (6.6+/-1.0 pg) and C6 (7.1+/-0.8 pg) cells incubated with SPIOF. The T2 signal intensity of U251 and C6 cells cultured with SPIOFC (233.6+/-25.9 and 211.4+/-17.2, respectively) were substantially lower than those of U251 and C6 cells incubated with SPIOF (2275.3+/-268.6 and 2342.7+/-222.4, respectively). Moreover, there were significant differences in iron per cell and T2 signal intensity between SPIOFC-treated neural cells (1.3+/-0.3; 2533.6+/-199.2) and SPIOFC-treated glioma cells. SPIOFC internalized by glioma cells exhibited green fluorescence by confocal laser scanning microscopy. CONCLUSION: SPIOFC is suitable for the specific and efficient targeting of glioma cells. MRI and optical imaging in conjunction with SPIOFC can differentiate glioma cells from normal brain tissue cells.
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Neoplasias Encefálicas/tratamento farmacológico , Meios de Contraste , Sistemas de Liberação de Medicamentos , Compostos Férricos/administração & dosagem , Glioma/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Nanopartículas Metálicas , Linhagem Celular Tumoral , HumanosRESUMO
BACKGROUND: Axonal regeneration in lesioned mammalian central nervous system is abortive, and this causes permanent disabilities in individuals with spinal cord injuries. This paper studied the action of neural stem cell (NSC) in promoting corticospinal axons regeneration and synapse reformation in rats with injured spinal cord. METHODS: NSCs were isolated from the cortical tissue of spontaneous aborted human fetuses in accordance with the ethical request. The cells were discarded from the NSC culture to acquire NSC-conditioned medium. Sixty adult Wistar rats were randomly divided into four groups (n = 15 in each): NSC graft, NSC medium, graft control and medium control groups. Microsurgical transection of the spinal cord was performed in all the rats at the T11. The NSC graft group received stereotaxic injections of NSCs suspension into both the spinal cord stumps immediately after transection; graft control group received DMEM injection. In NSC medium group, NSC-conditioned medium was administered into the spinal cord every week; NSC culture medium was administered to the medium control group. Hindlimb motor function was assessed using the BBB Locomotor Rating Scale. Regeneration of biotin dextran amine (BDA) labeled corticospinal tract was assessed. Differentiation of NSCs and the expression of synaptophysin at the distal end of the injured spinal cord were observed under a confocal microscope. Group comparisons of behavioral data were analyzed with ANOVA. RESULTS: NSCs transplantation resulted in extensive growth of corticospinal axons and locomotor recovery in adult rats after complete spinal cord transection, the mean BBB scores reached 12.5 in NSC graft group and 2.5 in graft control group (P < 0.05). There was also significant difference in BBB score between the NSC medium (11.7) and medium control groups (3.7, P < 0.05). BDA traces regenerated fibers sprouted across the lesion site and entered the caudal part of the spinal cord. Synaptophysin expression colocalized with BDA positive axons and neurons distal to the injury site. Transplanted cells were found to migrate into the lesion, but not scatter along the route of axon grows. The cells differentiated into astrocytes or oligodendrocytes, but not into the neurons after transplantation. Furthermore, NSC medium administration did not limit the degree of axon sprouting and functional recovery of the injured rats compared to the NSC graft group. CONCLUSIONS: Human embryonic neural stem cells can promote functional corticospinal axons regeneration and synapse reformation in the injured spinal cord of rats. The action is mainly through the nutritional effect of the stem cells on the spinal cord.
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Axônios/fisiologia , Neurônios/transplante , Tratos Piramidais/fisiologia , Traumatismos da Medula Espinal/cirurgia , Transplante de Células-Tronco/métodos , Sinapses/fisiologia , Animais , Comportamento Animal/fisiologia , Feminino , Humanos , Microscopia Confocal , Regeneração Nervosa , Neurônios/citologia , Tratos Piramidais/cirurgia , Distribuição Aleatória , Ratos , Ratos Wistar , Medula Espinal/fisiologia , Medula Espinal/cirurgiaRESUMO
OBJECTIVE: To evaluate the feasibility of monitoring the neural stem cells implanted into the brain by the technique of labeling with superparamagnetic iron oxide (SPIO). METHODS: Neural stem cells were isolated from the cerebral cortex of newborn Wister rats and cultured. SPIO particles and poly-L-lysine were added into the medium to be co-cultured foe one hour. After the formation of neurospheres, Prussian blue staining was conducted and transmission electron microscopy was used to identify the iron particles in these neural stem cells. Sixteen adult female Wistar rats underwent transplantation of labeled neural stem cells into the right side of brain and non-labeled cells were transplanted into the contralateral part as controls. 1, 2, 4, 6, and 7 weeks after the transplantation, MRI examination with the scanning sequences of SE T2WI, FSE T2WI, and GRE T2 * respectively was conducted on the brains of the rats. Four rats at each time point were killed and their brains were taken out to undergo HE staining and Prussian blue staining to track the presence of labeled-cells. RESULTS: After the addition of SPIO the neurospheres continued to proliferate and differentiate normally. Electron microscopy showed vacuolar structures of different sizes under the cytoplasma membrane within and outside which there were high-density iron particles. Prussian blue staining showed numerous blue stained particles in the cytoplasm of the labeled cells. Remarkable low signal change was seen in the right brain transplanted with labeled cells, especially in the condition of scanning sequence of GRET2. Such change could be seen up to 7 weeks after the transplantation. No signal change was found in the left brain. CONCLUSION: SPIO labeling technique is useful in monitoring the outcome of transplanted neural stem cells.