Predictive value of serum neurofilament light chain on neurologic function in out-of-hospital cardiac arrest patients / 中华急诊医学杂志

Objective:To determine the predictive value of serum neurofilament light chain (NfL) on neurologic function in out-of-hospital cardiac arrest (OHCA) patients.Methods:The clinical data of 96 OHCA patients admitted to Cangzhou Central Hospital from January 2018 to March 2022 were retrospectively analyzed. According to the Glasgow-Pittsburgh cerebral performance category (CPC) upon hospital discharge, the patients were divided into the favorable neurologic function (grade 1-2) and poor neurologic function (grade 3-5) groups. The difference of serum NfL was compared between the two groups, and the relationship between serum NfL and neurologic function was assessed using correlation analysis and logistic regression analysis. The area under the curve (AUC), sensitivity, and specificity of serum Nfl were calculated by receiver operating characteristic (ROC) curve. Hanley & McNeil method test was used to compare the difference of AUCs between serum NfL and neuron specific enolase (NSE).Results:Twenty-six percent (25/96) patients were discharged with favorable neurologic function. Serum NfL in the favorable neurological function group was significantly lower than that in the poor neurologic function group (47.6 pg/mL vs. 261.4 pg/mL, P<0.001). Correlation analysis showed that serum NfL was positively correlated with neurologic function ( r=0.69, P<0.001). Logistic regression analysis showed that serum NfL was independently associated with neurological function ( OR=0.92, 95% CI: 0.86-0.98; P=0.010). ROC curve indicated that the AUC of serum NfL in predicting poor neurologic function was 0.95 (95% CI: 0.92-0.99), with a sensitivity of 84.5% and a specificity of 100% at the cutoff value of 80.0 pg/mL. The AUC of serum NSE in predicting poor neurologic function was 0.79 (95% CI: 0.69-0.89), with a sensitivity of 67.6% and a specificity of 80.0% at the cutoff value of 45.1 ng/mL. A pairwise comparison using Hanley & McNeil method showed that the AUC of serum NfL in predicting poor neurologic function was higher than that of NSE ( Z=3.22, P=0.001). Conclusions:Serum NfL is helpful for clinician to predict neurologic function in OHCA patients.

TRPV4-induced Neurofilament Injury Contributes to Memory Impairment after High Intensity and Low Frequency Noise Exposures / 生物医学与环境科学（英文）

OBJECTIVE@#Exposure to high intensity, low frequency noise (HI-LFN) causes vibroacoustic disease (VAD), with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HI-LFN.@*METHODS@#Adult wild-type and transient receptor potential vanilloid subtype 4 knockout (TRPV4-/-) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN.@*RESULTS@#The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilament-positive nerve fibers in the cornu ammonis 1 (CA1) and dentate gyrus (DG) hippocampal areas in wild-type mice. However, TRPV4-/- mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure.@*CONCLUSION@#TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus, which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.

Clinical analysis of rapid eye movement sleep behavior disorder and plasma neurofilament light chain levels in patients with Parkinson's disease / 中华老年医学杂志

Objective:To investigate the relationship between rapid eye movement sleep behavior disorder(RBD)and neurofilament light chain(NfL)levels in patients with Parkinson's disease(PD).Methods:General clinical data of 121 PD patients and 38 healthy controls(HC)who visited the Department of Geriatric Neurology of the First Affiliated Hospital of Kunming Medical University from June 2019 to January 2021 were collected in a prospective study.According to the Rapid Eye Movement Sleep Behavior Disorder Questionnaire(RBDSQ), PD patients were divided into a PD with RBD group(PD-RBD, RBDSQ≥6)and a PD without RBD group(PD-NRBD, RBDSQ<6). General clinical data and plasma NfL levels of patients in the groups were compared.In addition, symptoms during exercise, during non-exercise, and sleep quality in the groups were also compared.Results:Plasma NfL levels were higher in the PD group than in the HC group(19.39 ng/L, 12.58-31.78; 14.85 ng/L, 9.78-22.15; Z=-2.492, P<0.05); plasma NfL levels were significantly higher in the PD-RBD group than in the PD-NRBD group and in the HC group(25.29 ng/L, 19.09-34.75; 17.14 ng/L, 11.70-26.67; 14.85 ng/L, 9.78-22.15; Z=-3.434, P<0.01); there was no significant difference in plasma NfL levels between the HC group and the PD-NRBD group( P>0.05). Receiver operating characteristic(ROC)curve analysis showed that, when the plasma NfL cutoff was set at 17.86 ng/L, PD-RBD and PD-NRBD could be distinguished( AUC=0.70, 95% CI=0.60-0.80, sensitivity 82%, specificity 54%). Binary logistic regression identified NfL level as an independent predictor of PD-RBD( β=0.068, OR=1.103, P=0.003). Conclusions:PD-RBD patients have increased plasma NfL levels, which can potentially serve as a biomarker for PD with RBD.

Research progress of neurofilament light chain in the parkinsonism / 中华神经科杂志

Neurofilament light chain (NfL), a sensitive biomarker of axonal damage, was found increasing in several neurological diseases. Parkinsonism is a group of clinical syndromes characterized by cardinal symptoms of bradykinesia, rigidity, and tremor, including Parkinson′s disease (PD) and parkinsonism plus syndrome (PPS). It is difficult in the diagnosis and differential diagnosis of PD and PPS, especially in the early stage. Evidence suggests that NfL in the cerebrospinal fluid and blood is a promising biomarker for the differential diagnosis of PD and PPS. This article reviewed and summarized the research progress of value of NfL in PD and PPS, and proposed future research directions.

Neuronal differentiation of rat bone marrow mesenchymal stem cells vialentivirus-mediated bone morphogenetic protein 7 transfection / 中国组织工程研究

BACKGROUND: Bone marrow mesenchymal stem cells have the potential to differentiate into neuron-like cells, which have been listed as the preferred stem cells for the treatment of spinal cord injury. However, due to their low differentiation efficiency, it is particularly important to find a factor with high induction ability. Based on literature review and our previous studies, it is speculated that bone morphogenetic protein 7 (BMP-7) gene may play a vital role in promoting the differentiation of bone marrow mesenchymal stem cells into neuron-like cells. OBJECTIVE: To investigate the differentiation of rat bone marrow mesenchymal stem cells into neurons induced by BMP-7 lentivirus vector transfection. METHODS: Bone marrow mesenchymal stem cells of Sprague-Dawley rats were cultured by whole bone marrow adherence method, and then were transfected with LV-GFP when multiplicities of infection were 50, 25, 10, and 1. Green fluorescent protein expression was observed using fluorescence inversion microscope in each group at 3 days after transfection, to confirm the best multiplicity of infection. Passage 3 bone marrow mesenchymal stem cells were divided into blank control group (routine culture), LV-GFP group, and LV-BMP-7-GFP group, followed by transfection at the best multiplicity of infection. After 24, 48, 72, 96, and 120 hours of transfection, MTT assay was used to detect cell survival rate in each group. Immunocytochemical assay was used to detect the expression of nerve cell markers (neurofilament protein 200, synaptophysin-1) after 3 days of transfection. RESULTS AND CONCLUSION: (1) After 3 days of LV-GFP transfection, GFP-positive cells were observed under fluorescence microscopy when multiplicities of infection were 10, 25, and 50, whereas no GFP-positive cells were found when the multiplicity of infection was 1. The average fluorescence intensity was the highest when the multiplicity of infection was 10 (P < 0.05), indicating that multiplicity of infection=10 had the best infection effect. (2) Immunocytochemical results showed that the expression of neurofilament-200 and synaptophysin-1 was negative in the blank control group and LV-GFP group, but positive in the LV-BMP-7-GFP group. The cell body and axon in the LV-BMP-7-GFP group were dyed bright brown. In summary, lentivirus-mediated BMP-7 transfection can promote the differentiation of rat bone marrow mesenchymal stem cells into neuron-like cells.

Neurofilament light chain in the assessment of patients with multiple sclerosis / Neurofilamento de cadeia leve na avaliação de pacientes com esclerose múltipla

ABSTRACT Multiple sclerosis (MS) is an autoimmune, inflammatory, and degenerative disease of the central nervous system. Axonal degeneration is triggered by inflammation and is the pathological substrate of progressive disability in patients with MS. Therapeutic interventions can reduce inflammatory activity, thus delaying neurodegeneration and the progression of disability. Disease activity and neurodegeneration are assessed mainly through clinical evaluation and magnetic resonance imaging. These measures lack sensitivity and accuracy, so new biomarkers are necessary. Several markers have been studied and to date the most promising is neurofilament light (NfL), a component of the axonal cytoskeleton, which is released into cerebrospinal fluid (CSF) following axonal damage. In the present study, we review the current knowledge about CSF NfL determination in MS, clinically isolated syndrome, and radiologically isolated syndrome, and critically discuss how CSF NfL measurement may contribute to therapeutic decision-making in these patients.

RESUMO A esclerose múltipla (EM) é uma doença autoimune, inflamatória e degenerativa do sistema nervoso central. A degeneração axonal é deflagrada pelo processo inflamatório e é o substrato patológico da incapacidade na EM. As intervenções terapêuticas reduzem a inflamação retardando a neurodegeneração e a progressão da incapacidade. A neurodegeneração é avaliada pelo quadro clínico e pela ressonância magnética. Estas mensurações não suficientemente acuradas, havendo necessidade de novos biomarcadores. Diversos biomarcadores têm sido estudados e, até o presente, o mais promissor é o neurofilamento de cadeia leve (NfL). O mesmo é um componente do citoesqueleto que é liberado no líquido cefalorraquidiano após injúria axonal. No presente estudo nós revisamos o conhecimento atual acerca do NfL na EM, síndrome clinica isolada e síndrome radiológica isolada, discutindo criticamente como a determinação deste biomarcador pode contribuir na tomada de decisões clínicas.

Effects of n-hexane on the serum level of three neurotoxicity biomarkers in rat / 中国职业医学

OBJECTIVE: To observe the effect of n-hexane subchronic exposure on the serum level of neuron specific enolase(NSE), neurofilament light chain protein(NF-L) and nerve growth factor(NGF) in rat, and to explore the feasibility of using NSE, NF-L and NGF as biomarkers of n-hexane neurotoxicity. METHODS: Specific pathogen free male SD rats were randomly divided into control group and low-, medium-and high-dose exposure groups, with 6 rats in each group. Rats in the low-, medium-and high-dose exposure groups were given n-hexane solution at doses of 168, 675 and 2 700 mg/kg body mass, respectively, while rats in the control group were gavaged with 0.9% sodium chloride solution, once a day, 5 days a week for 6 weeks. At week 0, 2, 4, and 6 of exposure, the body mass of the rats was weighed, the gait scores were performed, and the serum levels of NSE, NF-L, and NGF were detected.RESULTS: Body mass, gait score and serum levels of NSE and NF-L in rats were statistically significant in terms of the n-hexane exposure dose and exposure time(P<0.01). At the 6 th week of n-hexane exposure, the body mass of the three dose exposure groups was lower than that of the control group(P<0.05), and the gait score was higher than that of the control group(P<0.05). Moreover, the abnormal gait of the rats showed a dose-effect relationship with the increasing n-hexane poisoning dose. At week 2, 4 and 6, the serum levels of NSE and NF-L in these three dose exposure groups were higher than that in the control group(P<0.05). In addition, the serum level of NF-L in rats in the medium-and high-dose exposure groups increased with the n-hexane exposure time increasing and showed a time-effect relationship(P<0.05). The level of serum NGF in rats was statistically significant in the main effects of n-hexane dose and duration of exposure(P<0.05). The serum NGF level in the high-dose exposure group was lower than that in the control group, the low-dose and medium-dose exposure groups(P<0.05). NGF level in serum of rats at week 6 was lower than that at week 0, 2 and 4(P<0.05). CONCLUSION: Both NSE and NF-L in serum can be used as biomarkers for the early effect of n-hexane on peripheral nerve injury. The feasibility of using serum NGF as a biomarker for the early effect of n-hexane on peripheral nerve injury warrants further investigation.

Repair effect of bFGF combined with bone marrow mesenchymal stem cells on spinal cord injury in rats / 中国骨伤

OBJECTIVE@#To observe the repair effect of bone marrow mesenchymal stem cells (BMSCs) combined with basic fibroblast growth factor (bFGF) on spinal cord injury in rats and explore its mechanism.@*METHODS@#SD rat BMSCs were obtained by serum culture technique. Eighty healthy 6-week-old male SD rats(weight about 240 g) were randomly divided into 4 groups with 20 each. The sham operation group underwent simple laminectomy without damaging spinal cord and was kept in the same condition as the other 3 groups. The other 3 groups underwent left T9 spinal cord hemisection to establish spinal cord injury model. After 9 days of modeling the local transplantation was performed. The Control group was implanted with gelatin sponge containing normal saline. The BMSCs transplantation group was implanted with gelatin sponge containing BMSCs. The bFGF+BMSCs transplantation group was implanted with gelatin sponge containing bFGF+BMSCs. After 4 and 8 weeks, the expression of NF-200 and GFAP in injured spinal cord tissue was analyzed by Western blotting and the recovery of hind limb function was evaluated by Basso Beattie Bresnahan(BBB) motor function score scale.@*RESULTS@#The BBB scores of BMSCs transplantation group and bFGF+BMSCs transplantation group were better than control group at 4 and 8 weeks after operation (<0.05) and there was significant difference between bFGF+BMSCs transplantation group and BMSCs transplantation group (<0.05). After 4 and 8 weeks postoperatively, NF-200 expression was minimal in control group and only a small amount was expressed in BMSCs transplantation group while in bFGF+BMSCs transplantation group NF-200 was highly expressed(<0.05). GFAP expression was high in control group, middle in BMSCs transplantation group and low in bFGF BMSCs transplantation group(<0.05). There was significant difference between bFGF+BMSCs transplantation group, BMSCs transplantation group and control group(<0.05).@*CONCLUSIONS@#The combined transplantation of BMSCs and bFGF can repair the spinal cord injury in rats. The mechanism may be related to the decrease of GFAP expression and the increase of NF-200 expression.

Three-vessel coronary artery disease may predict changes in biochemical brain injury markers after off-pump coronary artery bypass grafting / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Neurological injury is a frequent and important complication of coronary artery bypass grafting (CABG). Several risk factors for this type of sequela have been identified, among them aortic arch atherosclerosis. Our previous study indicated that atherosclerotic burden in coronary arteries may likewise predict postoperative neurological complications (Pawliszak et al., 2016b). We assessed the severity of this condition by using the SYNTAX score calculator. However, diagnosing angiographic three-vessel coronary artery disease (3VD) could be an even simpler method of achieving this goal.

Interleukin-6, S-Nitrosothiols, and Neurodegeneration in Different Central Nervous System Demyelinating Disorders: Is There a Relationship?

BACKGROUND AND PURPOSE: A few groups have suggested that activated cytokines and nitrosative stress are closely involved in the pathogenesis of different demyelinating disorders induced by the neuroinflammatory destruction of neurons. The purpose of this study was to elucidate the associations of cytokines and S-nitrosothiols (RSNO) with the severity of neurodegeneration during relapse in demyelinating disorders of the central nervous system. METHODS: We measured levels of interleukin-6 (IL-6), erythropoietin, RSNO, and phosphorylated neurofilament heavy chain (pNfh) in cerebrospinal fluid (CSF) samples obtained from patients with different demyelinating disorders: multiple sclerosis (MS, n=52), acute disseminated encephalomyelitis (ADEM, n=9), and neuromyelitis optica spectrum disorders (NMOSD) with aquaporin-4 immunoglobulin G (AQP4-IgG, n=12). We compared these levels with those measured in a control group (n=24). RESULTS: We found that IL-6 in CSF was elevated in NMOSD with AQP4-IgG and ADEM patients as well as in MS patients after the destruction of soluble IL-6. Erythropoietin levels were lower in MS, while RSNO levels were higher in NMOSD with AQP4-IgG and MS patients than in the control group. CSF pNfh levels were elevated in MS and ADEM patients. CONCLUSIONS: These results confirm that IL-6 is activated in different demyelinating disorders, with this elevation being more prominent in the CSF of NMOSD with AQP4-IgG and ADEM patients. Moreover, S-nitrosylation is activated in demyelinating disorders with spinal-cord injury and neurodegeneration in these patients. However, we found no correlation between these biochemical markers, and so we could not confirm whether IL-6-mediated nitric oxide production is involved in spinal-cord lesions.

The cerebrospinal fluid in multiple sclerosis: far beyond the bands / O líquido cefalorraquidiano na esclerose múltipla: muito além das bandas

ABSTRACT The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency. A more refined evaluation of disease and therapy status can contribute to better therapeutic choices, particularly in escalation of therapies. This is very relevant taking into account the availability of a greater number of drugs for multiple sclerosis treatment in recent years. In this review, we critically evaluate the current literature regarding the most important cerebrospinal fluid biomarkers in multiple sclerosis. The determination of biomarkers levels, such as chemokine ligand 13, fetuin A, and mainly light neurofilament has shown promising results in the evaluation of this disease, providing information that along with clinical and neuroimaging data may contribute to better therapeutic decisions.

RESUMO A análise do líquido cefalorraquidiano tem sido empregada para avaliação diagnóstica da esclerose múltipla e a exclusão dos diagnósticos diferenciais. Os achados clássicos refletem a natureza inflamatória da doença, incluindo discreta pleocitose, leve hiperproteinorraquia, aumento da síntese intratecal de imunoglobulina G e, mais tipicamente, a presença de bandas oligoclonais. Nos últimos anos, surgiram novos biomarcadores para esclerose múltipla, e esta busca por marcadores reflete a necessidade de melhor avaliar a atividade e a progressão da doença, bem como a eficácia terapêutica. Uma avaliação mais refinada da atividade da doença e da resposta aos medicamentos pode contribuir para melhores decisões terapêuticas, particularmente no que se refere à troca de medicação. Isto é muito importante nos dias de hoje, quando surgem novas opções medicamentosas. Neste artigo de revisão, avaliamos criticamente a literatura atual referente aos novos marcadores liquóricos na esclerose múltipla. A mensuração destes marcadores, como a quimiocina CXCL13, fetuína A e, principalmente, o neurofilamento de cadeia leve, demonstrou resultados promissores na avaliação da doença, provendo informações que, em conjunto com dados clínicos e de neuroimagem, podem contribuir para melhores decisões terapêuticas.

Intermittent starvation attenuating neurofilament phosphorylation and spatial learning and memory disorder induced by sodium nitrite in rats / 解剖学报

Objective To explore the effect of intermittent starvation on neurofilament phosphorylation and spatial learning and memory in rats induced by sodium nitrite. Methods Thirty-six rats were randomly divided into control, NaNO2 and stavation + NaNO2 groups, 12 rats in each group. NaNO2 group and slavation + NaNO2 group rats were served as drinking water containing sodium nitrite [100mg/(kg · d)]. Starvation + NaNO2 group rats were deprived of food for 2 days, and then re-feeded for 3 days. Sixty days later, the ability of spatial learning and memory of the rats was measured by Morris water maze. Phosphorylation level of neurofilament in the hippocampus was detected by immunohistochemistry and Western blotting. Results In comparison with the control rats, the NaNO2 rats showed significantly longer latency to find the hidden platform from 2 days to 7 days in Morris water maze (control group latency: 31.24 ± 8.53, 12.41 ± 6.54, 10.49 ± 6.43, 8.61 ±2.56, 7.25 ±2.12, 6.03 ±1.92; NaNO2 group latency: 53.34 ±5.28, 35.15 ± 10.29, 23.52 ±9.50, 14.49 ±8.70, 16.87 ±8.77, 12.31 ±7.12) (P<0.05, P <0.01), and elevated phosphorylation level of neurofilament, while stavation + NaNO2 group rats only showed longer latency on 2 days and 3 days(43.61 ± 1.76, 25.25 ±7.49) in Morris water maze. There was no obvious difference in phosphorylation level of neurofilament between the control and stavation + NaNO2 group. Conclusion Intermittent starvation attenuates neurofilament phosphorylation and spatial learning and memory disorder induced by sodium nitrite in rats.

Effects of quercetin on glial scar formation and axonal regeneration after acute spinal cord injury in rats and its association with p38 mitogen activated protein kinase signal pathway / 中华创伤骨科杂志

Objective To investigate the effects of quercetin on glial scar formation and axonal regeneration after spinal cord injury (SCI) and its association with the p38 mitogen activated protein kinase (MAPK) signal pathway.Methods 128 female Sprague-Dawley (SD) rats were randomly divided into a control group (SCI + saline),an intervention group (SCI + quercetin + anisomycin),a treatment group (SCI + quercetin) and a sham-operation group (n =32).Basso Beattie Bresnahan (BBB) assessment and footprint analysis of the hind limb were performed on days 1,3,7,14,21 and 28 postoperation in each group.The expression levels of p38MAPK,phosphorylation p38MAPK,glial fibrillary acidic protein (GFAP) and neurofilament protein-200 (NF-200) were detected by Western blot.The numbers of GFAP and NF-200 positive staining cells in the injured spinal cord in each group were detected by immunohistochemistry.Results The BBB scores in the treatment group were significantly higher than in the intervention and control groups at each time point after SCI except on day 3 postoperation (P ＜ 0.05).The expression levels of phosphorylation p38MAPK protein in each SCI group were significantly higher than in the sham-operation group on days 3 and 7 postoperation (P ＜ 0.05).The expression levels of phosphorylation p38MAPK protein in the treatment group were significantly lower than in the control and intervention groups on days 3,7 and 14 postoperation (P ＜ 0.05),but there was no significant difference on day 28 postoperation among all the groups (P ＞ 0.05).The numbers of NF-200 and GFAP positive staining cells were significantly greater than in the sham-operation group at each time point postoperation (P ＜ 0.05);the NF-200 positive staining cells in the treatment group were significantly increased in comparison with the control and intervention groups (P ＜ 0.05);the GFAP positive staining cells in the treatment group were significandy fewer than in the control and intervention groups on days 7,14 and 28 postoperation (P ＜ 0.05).Conclusions Quercetin may have protective effects against acute SCI by decreasing glial scar formation,increasing axonal regeneration and promoting recovery of locomotor and nerve function in rats.The effects may be correlated with inhibition of the p38MAPK signal pathway.

Significance of neurofilament light in the diagnosis and prognosis of neuromyelitis optica spectrum disorders / 中华神经科杂志

Objective To discover the significance of neurofilament light (NFL) chain of cerebrospinal fluid (CSF), an axonal injury biomarker, in diagnosis and prognosis prediction of neuromyelitis optica spectrum disorders(NMOSD).Methods Sixty-one NMOSD patients and 24 other patients such as neurosis, migraine and so on, with lumbar puncture were enrolled as NMOSD group and normal control (NC) group from in and out patients of Department of Neurology of Navy General Hospital from January 2014 to August 2016. The clinical and neuroimaging features of NMOSD group and CSF samples of both groups were collected,and the NFL levels of CSF were measured by enzyme linked immunosorbent assay. The CSF NFL levels in different subtypes of NMOSD patients were compared, and the influence factors of the NFL levels in CSF were calculated by multiple linear regression analysis. Results The NFL levels of CSF in NMOSD group (2 729.00(14 862.00) pg/ml) were significantly higher than that in NC group ((299.50(308.00) pg/ml, t=8.588, P=0.000;t test of NFL levels was performed after logarithmicly transforming based on 10). There were no statistically significant differences of CSF NFL levels among optic neuritis, longitudinally extensive transverse myelitis and neuromyelitis optica. In NMOSD group, age (b=0.017, P<0.01), Expanded Disability Status Scale score (b=0.078, P<0.05) and enhancement in gadolinium-magnetic resonance imaging (b=0.478, P<0.01) were correlated with the NFL levels of CSF, while gender, courses of diseases and aquaporin 4 antibody in serum were not related to the NFL levels. Conclusion The NFL levels of CSF are conducive to assess the severity and probable progress of NMOSD.

Correlation between Serum Phosphorylated High-molecular-weight Neurofilament and Severity of Spinal Cord Injury in Rats / 中国康复理论与实践

Objective To investigate the level of phosphorylated high-molecular-weight neurofilament (pNF-H) after spinal cord injury (SCI), and explore the relationship between pNF-H and severity of SCI. Methods 20 Sprague-Dawley rats were equally divided into control group (group A), mild SCI group (group B), moderate SCI group (group C) and severe SCI group (group D). The level of pNF-H in serum, BBB score and remaining area of white matter were obtained at different time points. Results The level of serum pNF-H in groups B, C and D arrived at peaks 12 hours and 3 days after SCI, and there was significant difference among them (P<0.05). Both BBB score and remaining area of white matter 14 days after SCI negatively correlated with the level of pNF-H 3 days after SCI (r=-0.987 and r=-0.978, respective-ly). Conclusion The pNF-H increases twice after SCI in rats, and may be associated with the severe of SCI, which can be considered as a biomarker.

Innervation in women with uterine myoma and adenomyosis

OBJECTIVE: To determine if neurofilament (NF) is expressed in the endometrium and the lesions of myomas and adenomyosis, and to determine their correlation. METHODS: Histologic sections were prepared from hysterectomies performed on women with adenomyosis (n=21), uterine myoma (n=31), and carcinoma in situ of the uterine cervix. Full-thickness uterine paraffin blocks, which included the endometrium and myometrium histologic sections, were stained immunohistochemically using the antibodies for monoclonal mouse antihuman NF protein. RESULTS: NF-positive cells were found in the endometrium and myometrium in 11 women with myoma and in 7 with adenomyosis, but not in patients with carcinoma in situ of uterine cervix, although the difference was statistically not significant. There was no significant difference between the existence of NF-positive cells and menstrual pain or phases. The NF-positive nerve fibers were in direct contact with the lesions in nine cases (29.0%) of myoma and in five cases (23.8%) of adenomyosis. It was analyzed if there was a statistical significance between the existence of NF positive cells in the endometrium and the expression of NF-positive cells in the uterine myoma/adenomyosis lesions. When NF-positive cell were detected in the myoma lesions, the incidence of NF-positive nerve cells in the eutopic endometrium was significantly high. When NF-positive cell were detected in the basal layer, the incidence of NF-positive nerve cells in the myoma lesions and adenomyosis lesions was significantly high. CONCLUSION: We assume that NF-positive cells in the endometrium and the myoma and adenomyosis lesions might play a role in pathogenesis. Therefore, more studies may be needed on the mechanisms of nerve fiber growth in estrogen-dependent diseases.

The protective effects of gastrodin on the brain injury and the integrity of myelin in striatum after cerebral ischemia-reperfusion in mice / 中华行为医学与脑科学杂志

Objective To investigate the effects of gastrodin on neural function and the expression of myelin basic protein (MBP) and neurofilament high molecular weight (NFH) in the striatum during cerebral ischemiareperfusion in mice.Methods 36 Kunming mice were randomly divided into sham group,MCAO group and gastrodin (GAS) group.The middle cerebral artery occlusion(MCAO) was established by artery embolization.The mice in sham group were received fake surgery and saline,and the mice in MCAO and GAS group were exposed to MCAO,and received saline and GAS (100 mg/(kg · d)) injection,respectively,immediately after the operation for 7 days.On the 8th day of operation,the neurological severity scores of the mice were observed and the volume ratio of the cerebral infarction was estimated by triphenyl tetrazolium chloride (TTC) staining.Immunohistochemistry was used to detect the MBP and NF-H in the striatum.Results (1) The mice in MCAO group showed significant neurologic deficient in comparison with sham group,and the neurological severity scores of gastrodin group(3.13±0.64) were significantly higher than that(1.38±0.52) of MCAO group (P＜0.05).(2) Results of TTC staining showed that the infarction volume was obviously larger in the injured cerebral tissue in MCAO group in comparison with sham group,and the volume ratio of the cerebral infarction significantly decreased after the intervention with GAS (P＜0.05).(3) The integral optical density of MBP(272968.14±1215.23) and NF-H(12 142.73±47.16) in MCAO group decreased as compared to that((43 855.23±2434.16),(275 321.00±926.15)) in sham group and GAS group((321 531.2±2376.14),(106 135.73±598.15)) (P＜0.05).Conclusion GAS can improve neural function of mice after middle cerebral artery occlusion,and it may play an important role in protecting myelin and nerve fibers of striatum.

Characterization of a murine neuron-enriched model of primary trigeminal ganglia cultures to study the interferon-ß antiviral effect against Herpes Simplex Virus type 1 / Caracterización de un modelo murino de cultivos primarios de ganglio trigeminal enriquecido en neuronas para el estudio del efecto antiviral del interferón-ß frente al virus Herpes simple tipo 1

Objective: To characterize a neuron-enriched primary TG culture and evaluate interferon- β expression and activity after HSV-1 infection. Materials and methods: The percentage of neurons present in cultures was assessed by neurofilament immunocytochemistry. Cultures were treated with interferon- β and infected with HSV-1, then viral antigen positive cells were counted and interferon- βexpression was assessed by quantitative PCR. Results: The culture contained 15% neurons and 85% non-neuronal cells. A cytopathic effect was observed, associated with high viral spread (72.9% neurons and 48.3% non-neuronal cells were positive for viral antigen). Interferon- β treatment impaired the cytopathic effect and decreased the infected neurons to 16.7% and infected non-neuronal cells to 7.8%. Viral infection at 6 h postinfection significantly increased the interferon- β transcripts by 18.2 fold, while at 18 h postinfection Interferon pre-treatment in infected cultures increased interferon- β transcription by 3.7 fold. Discussion: This culture model contained 15% neurons, which is 10 times higher compared to other reported cultures, and non-neuronal cells comprised 85% of cells in this culture. All types of cells were found to be infected, which is similar to that reported during acute infections in vivo . Additionally, interferon- βdecreased the infected cells, avoiding the cytopathic effect, which is similar to that reported in swine TG cultures. Conclusions: A neuron-enriched primary TG model was characterized. Interferon- β treatment protected cells from cytopathic effects and viral spread, while viral infection up-regulated interferon- β expression. This result means that interferon- β exerts an important antiviral effect against HSV-1 in these cultures.

Objetivo: Caracterizar un cultivo primario de ganglio trigeminal (GT) enriquecido en neuronas y evaluar la expresión de interferón- y su actividad frente a la infección con Herpes simple tipo 1 (HSV-1). Materiales y métodos: El porcentaje de neuronas fue determinado por inmunocitoquímica para neurofilamento. Los cultivos fueron tratados con interferón- β e infectados con HSV-1, y se cuantificaron las células positivas para antígeno viral por inmunocitoquímica y la expresión de interferón- β por PCR cuantitativa. Resultados: El cultivo presentó un 15% de neuronas y 85% de células no neuronales. Se encontró efecto citopático, asociado a una alta diseminación de la infección (72,9% neuronas y 48,3% de células no neuronales positivas para antígeno viral). El interferón- β evitó la aparición de efecto citopático y disminuyó las células infectadas a 16,7% en neuronas y a 7,8% las células no neuronales. La infección viral incrementó la expresión de transcritos de interferón- β 18,2 veces a las 6 h de infección, mientras que a las 18 h post infección el tratamiento con interferón incrementó esta expresión 3,7 veces. Discusión: Los cultivos presentaron un 15% de neuronas, lo cual es 10 veces más que en otros cultivos reportados. Las células no neuronales representan el 85% de las células del cultivo, y se evidenció que todos los tipos de células se infectaron; similar a lo que ha sido reportado durante infecciones agudas in vivo . Adicionalmente, el interferón- β disminuyó el porcentaje de células infectadas y evitó la aparición de efecto citopático, similar a lo que ha sido reportado en cultivos de GT porcino. Conclusiones: Se caracterizó un modelo de cultivo primario de GT enriquecido en neuronas. Interferón- β protegió las células del efecto citopático y la diseminación viral mientras que la infección viral incrementó la expresión de interferón- β. Por lo tanto, el interferón- β ejerció un papel antiviral importante frente al HSV-1 en estos cultivos.

Effect of GPR56 on axonal development and myelination / 中华急诊医学杂志

Objective To determine the likelihood of G-protein coupled receptor 56 (GPR56 ) induces axonal development and myelination in the corpus callosum of mouse brain.Methods A total of 64 Gpr56 +/-and Gpr56 -/-mice were selected and randomly divided into two groups:Gpr56 +/-group (n=32)and Gpr56 -/-group (n=32).According to number of days after birth,each group was further divided into 4 subgroups including P7d,P14d,P21d and P28d subgroups.Levels of neurofilament-200 (NF -200)and proteolipid protein (PLP ) of myelin basic protein in corpus callosum were measured with immunohistochemistry staining and Western blot in P7d、P14d、P21d、P28d Gpr56 +/- and Gpr56 -/-mice.Gpr56 +/-and Gpr56 -/-neurons were cultured using P1 d Gpr56 +/-and Gpr56 -/-mouse brain.The lengths of Gpr56 +/- and Gpr56 -/-neuronal axon were measured and compared with Image J software. Axonal myelination in the corpus callosum of mouse brain in each group was observed under electronic microscopy and the axonal diameters between subgroups were compared.Results The levels of NF-200 and PLP in the corpus callosum in P7d、P14d、P21d、P28d Gpr56 -/-mice decreased significantly compared with Gpr56 +/- mice.The length of Gpr56 -/-neuronal axon was shortened compared with Gpr56 +/-neuronal axon.The number of myelinated axons was obviously reduced in the corpus callosum in P28d Gpr56 -/-mice.The diameter of axon in the corpus callosum of P28d Gpr56 +/-mouse is longer than that of P28d Gpr56 -/-mouse. Conclusions GPR56 may be involved in axonal development and myelination in the corpus callosum of mouse brain.

Expression of neurofilament protein and synaptophysin in the developing spinal cord of human embryo / 解剖学报

Objective To investigate the neurofilament protein (NF) and synaptophysin(SYN) distribution in the developing stage of human embryonic spinal cord and their clinical significance . Methods Totally 16 of human embryos, aged from 2 to 4 months were used in this study .Immunohistochemical staining was uesd to detect the expression and distribution of NF and SYN in the spinal cord .Results At the second month stage , NF expression was weakly positive in only the marginal layer on both sides of the spinal cord .At 3-4 months, NF expression was positive or strong positive in the spinal cord center crack before and after the middle of partition and cortex .In the ependymal layer of the lateral part of the expression of NF positive nerve fibers were seen in the gray matter .From 2 to 4 month-age, all visible SYN positive expressions distributed in the spinal cord .With the increase of gestational age , SYN positive expression in the spinal cord staining intensity value was increased first , and then decreased .The number of positive values increased month by month . Conclusion NF and SYN both take part in the regulation of human embryonic spinal cord tissue growth .