Objective:Optic nerve glioma (ONG) is a rare disease, defined as a WHO grade I tumor, which affects the visual pathway. The objective of this study was to investigate the expression of miR-223-3p in ONG as well as its function and regulation in ONG cell lines.Methods:qRT-PCR assays were used to measure miR-223-3p expression in ONG tissues and cell lines. After overexpression of miR-223-3p in Hs683 and WERI-Rb-1 cell lines, CCK-8 and EdU assays were performed to examine cell proliferation, and flow cytometry was used to assess apoptosis. Dual luciferase assays were utilized to identify the target binding to miR-223-3p and NLRP3. Rescue assays were carried out to investigate the regulatory mechanism of miR-223-3p acting through NLRP3. Nude mouse tumorigenesis assays were established to verify the effect of miR-223-3p on ONG growth.Results:miR-223-3p was weakly expressed in both ONG tissues and cell lines. miR-223-3p inhibited the proliferative ability of Hs683 and WERI-Rb-1 cell lines and promoted apoptosis. In addition, there was binding between miR-223-3p and NLRP3. Simultaneous overexpression of NLRP3 and miR-223-3p partially counteracted the role of miR-223-3p in the cell lines. Lastly, miR-223-3p inhibited ONG growth.Conclusion:miR-223-3p plays an inhibitory role in ONG development by regulating NLRP3 to inhibit the proliferation of ONG cells and promote apoptosis.

Optic neuritis (ON) is a common neurological disease, and the transplant of retinal ganglion cells (RGCs) has been thought as a promising strategy for improving the injury of the optic nerve system. Bone mesenchymal stem cells (BMSCs) have the potential to differentiate into neural cells. Several studies have indicated that GAP-43 is related with the regeneration of nerve cells, while the effect of GAP-43 on inducing BMSC differentiation remains unclear. In this study, the BMSCs were separated from the rats and identified with flow cytometry assay. The GAP-43 expressed vectors were transfected into the BMSCs, and the biomarkers of RGCs such as PAX6, LHX2, and ATOH7 were used to observe by qRT-PCR. Moreover, the effect of GAP-43-induced BMSCs (G-BMSCs) on ON improvement was also verified with rat models, and the activity of MAPK pathway was measured with western blot. Here, it was found that GAP-43 could obviously promote the differentiation of BMSCs, and increased PAX6, LHX2, ATOH7, BRN3A, and BRN3B were observed in the process of cell differentiation. Moreover, it was also found that G-BMSCs significantly increased the abundances of NFL and NFM in G-BMSCs, and GAP-43 could also enhance the activity of MAPK pathways in BMSCs. Therefore, this study suggested that GAP-43 could induce the differentiation of bone marrow-derived mesenchymal stem cells into retinal ganglial cells.

Objective. Present study mainly explored the effect of miR-216b-5p on experimental optic neuritis and mechanism. Methods. Female C57BL/6 mice were utilized to establish the EAE model. miR-216b-5p expression was measured by RT-qPCR. Protein expression was evaluated via western blot. Inflammatory infiltration score was analyzed by HE staining. Visual function was assessed by measuring the OKR. Flow cytometry assay was conducted to measure the percentage of IL-17 cells. ELISA was utilized to evaluate the immune factor. Results. The EAE mouse model was successfully established. The EAE score of mice began to increase in EAE group after 11 days of MOG35-55 and CFA immunization. The degree of inflammatory cell infiltration in EAE mice was higher than that in normal mice. Compared with normal mice, the number of microglia and astrocytes was raised in EAE mice. miR-216b-5p expression was obviously declined and FAS expression was obviously raised in EAE. Compared with NC group, demyelination scores and axonal loss were markedly declined in miR-216b-5p mimic group. IL-17A concentration and the percentage of IL-17 cells were obviously declined in miR-216b-5p mimic group. FAS was predicted to be regulated by miR-216b-5p by TargetScan, and luciferase reporter assay confirmed this prediction. In addition, overexpression of FAS exacerbated experimental optic neuritis by promoting the inflammatory response and Th17 cell differentiation, and miR-216b-5p reversed this effect. Conclusions. miR-216b-5p downregulated FAS and inhibited the progression of experimental optic neuritis via promoting the inflammatory response and Th17 cell differentiation.

Optic neuritis (ON) is a common neurological disease, and the transplant of retinal ganglion cells (RGCs) has been thought as a promising strategy for improving the injury of the optic nerve system. Bone mesenchymal stem cells (BMSCs) have the potential to differentiate into neural cells. Several studies have indicated that GAP-43 is related with the regeneration of nerve cells, while the effect of GAP-43 on inducing BMSC differentiation remains unclear. In this study, the BMSCs were separated from the rats and identified with flow cytometry assay. The GAP-43 expressed vectors were transfected into the BMSCs, and the biomarkers of RGCs such as PAX6, LHX2, and ATOH7 were used to observe by qRT-PCR. Moreover, the effect of GAP-43-induced BMSCs (G-BMSCs) on ON improvement was also verified with rat models, and the activity of MAPK pathway was measured with western blot. Here, it was found that GAP-43 could obviously promote the differentiation of BMSCs, and increased PAX6, LHX2, ATOH7, BRN3A, and BRN3B were observed in the process of cell differentiation. Moreover, it was also found that G-BMSCs significantly increased the abundances of NFL and NFM in G-BMSCs, and GAP-43 could also enhance the activity of MAPK pathways in BMSCs. Therefore, this study suggested that GAP-43 could induce the differentiation of bone marrow-derived mesenchymal stem cells into retinal ganglial cells.

Objective . Present study mainly explored the effect of miR-216b-5p on experimental optic neuritis and mechanism. Methods . Female C57BL/6 mice were utilized to establish the EAE model. miR-216b-5p expression was measured by RT-qPCR. Protein expression was evaluated via western blot. Inflammatory infiltration score was analyzed by HE staining. Visual function was assessed by measuring the OKR. Flow cytometry assay was conducted to measure the percentage of IL-17 cells. ELISA was utilized to evaluate the immune factor. Results . The EAE mouse model was successfully established. The EAE score of mice began to increase in EAE group after 11 days of MOG35-55 and CFA immunization. The degree of inflammatory cell infiltration in EAE mice was higher than that in normal mice. Compared with normal mice, the number of microglia and astrocytes was raised in EAE mice. miR-216b-5p expression was obviously declined and FAS expression was obviously raised in EAE. Compared with NC group, demyelination scores and axonal loss were markedly declined in miR-216b-5p mimic group. IL-17A concentration and the percentage of IL-17 cells were obviously declined in miR-216b-5p mimic group. FAS was predicted to be regulated by miR-216b-5p by TargetScan, and luciferase reporter assay confirmed this prediction. In addition, overexpression of FAS exacerbated experimental optic neuritis by promoting the inflammatory response and Th17 cell differentiation, and miR-216b-5p reversed this effect. Conclusions . miR-216b-5p downregulated FAS and inhibited the progression of experimental optic neuritis via promoting the inflammatory response and Th17 cell differentiation.

Objective . Optic nerve glioma (ONG) is a rare disease, defined as a WHO grade I tumor, which affects the visual pathway. The objective of this study was to investigate the expression of miR-223-3p in ONG as well as its function and regulation in ONG cell lines. Methods . qRT-PCR assays were used to measure miR-223-3p expression in ONG tissues and cell lines. After overexpression of miR-223-3p in Hs683 and WERI-Rb-1 cell lines, CCK-8 and EdU assays were performed to examine cell proliferation, and flow cytometry was used to assess apoptosis. Dual luciferase assays were utilized to identify the target binding to miR-223-3p and NLRP3. Rescue assays were carried out to investigate the regulatory mechanism of miR-223-3p acting through NLRP3. Nude mouse tumorigenesis assays were established to verify the effect of miR-223-3p on ONG growth. Results . miR-223-3p was weakly expressed in both ONG tissues and cell lines. miR-223-3p inhibited the proliferative ability of Hs683 and WERI-Rb-1 cell lines and promoted apoptosis. In addition, there was binding between miR-223-3p and NLRP3. Simultaneous overexpression of NLRP3 and miR-223-3p partially counteracted the role of miR-223-3p in the cell lines. Lastly, miR-223-3p inhibited ONG growth. Conclusion . miR-223-3p plays an inhibitory role in ONG development by regulating NLRP3 to inhibit the proliferation of ONG cells and promote apoptosis.

脑胶质瘤( Glioma )是最常见的颅内肿瘤〔1〕,约占颅内原发肿瘤的一半,其恶性率是全身肿瘤的2％ ～3％ 〔2〕.Glioma 可分为低级别胶质瘤和高级别胶质瘤.高级别胶质瘤具有迅速性侵袭生长、血管不正常增生、容易破坏脑组织等生物学特性,这使得恶性胶质瘤治疗难度大,且预后较差.胶质母细胞瘤( GBM)是常见的脑恶性肿瘤,经过系统治疗后其中位生存时间仍少于15个月〔3,4〕.目前,GBM经过手术、放化疗等治疗后效果仍达不到患者及家属的心理预期.本文对Glioma治疗现状及临床进展进行综述.

Objective To investigate the effects of interleukin-2 ( IL-2 ) activated NK cells on gliomas in animal models. Methods The nude mice were divided into seven groups. A:sterile nude mice control group;B:in vivo transplan-tation GBM group;C:in vivo injection of IL-2 group;D:injection of NK cells group;E:simultaneous transplantation of BGM tissue and NK cells group;F:simultaneous transplantation of IL-2 and NK cells group;G:simultaneoustransplantation of BGM,NK cells and IL-2 group. To observe the growth of nude mice,the growth of tumor in nude mice,the emergence time of the tumor,the growth of the tumor ( size and weight) data etc,and carry out statistical analysis. Results NK cells have hadinhibition and killing effect on GBM,and IL-2 can promote the inhibition and killing effect of NK cells on GBM,and can coulddelay the growth of glioma. Conclusion NK cells have the effect of inhibiting the human brain glioma and lay the foundation for the clinical immunotherapy of glioma.

Aortic dissection is a devastating disease with protean clinical manifestations. Given the high mortality within the initial few hours after onset, it is important to maintain a high level of suspicion for this diagnosis. Guillain-Barre syndrome (GBS) is an autoimmune disorder of the peripheral nervous system and is the most common cause of acute flaccid paralysis since the worldwide eradication of poliomyelitis. Here, we report on a 55-year-old woman who presented with aortic dissection-induced paraplegia and respiratory distress resembling the ascending flaccid paralysis of GBS. The patient had complained of progressive weakness of the lower extremities for 4 days. Ascending flaccid paralysis of GBS was suspected. However, chest computed tomography revealed expansion of the aorta with visible dissection, and acute aortic dissection was diagnosed. In conclusion, aortic dissection might be misdiagnosed due to its protean manifestations.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare chronic inflammatory disorder in the central nervous system (CNS), which is characterized by magnetic resonance imaging (MRI) appearance with punctate and curvilinear gadolinium enhancement "peppering" the pons. Lesions of CLIPPERS mainly involve the pons and the cerebellum. Adjacent structures such as the medulla and the midbrain may also be involved. It is proposed that CLIPPERS is an immune-mediated inflammatory condition characteristic of T-cell-predominant infiltrates and good responsiveness to corticosteroids.We report a 46-year-old woman who presented with horizontal eyeball akinesia and gait ataxia with characteristic MRI features of CLIPPERS. The possible pathogenesis, clinical manifestations, imaging features, treatment, and prognosis of this peculiar disorder are summarized.This report contributes to the clinical understanding of CLIPPERS which may present with horizontal eyeball akinesia as an initial manifestation. The characteristic presentation of a subacute cerebellar and brainstem syndrome and pepper-like gadolinium enhancement was confirmed in this report. Long-term immunosuppressive treatment seems to be mandatory to sustain improvement. Azathioprine alone may be capable of maintaining remission.

Considerable evidence has demonstrated that metformin can activate 5'-AMP-activated protein kinase (AMPK) signaling pathway, which plays a critical role in protection of endothelial cell permeability. Hence, the present study evaluated the effects of metformin on blood brain barrier permeability and AQP4 expression in vitro, and assessed the effects of metformin treatment on tumor-induced brain edema in vivo. Hypoxia or VEGF exposure enhanced bEnd3 endothelial cell monolayer permeability and attenuated the expression of tight junction proteins including Occludin, Claudin-5, ZO-1, and ZO-2. However, 0.5 mM metformin treatment protected bEnd3 endothelial cell monolayer from hypoxia or VEGF-induced permeability, which was correlated with increased expression of tight junction proteins. Furthermore, metformin treatment attenuated AQP4 protein expression in cultured astrocytes. Such an effect involved the activation of AMPK and inhibition of NF-κB. Finally, metformin treatment dose-dependently reduced glioma induced vascular permeability and cerebral edema in vivo in rats. Thus, our results suggested that metformin may protect endothelial cell tight junction, prevent damage to the blood brain barrier induced by brain tumor growth, and alleviate the formation of cerebral edema. Furthermore, since the formation of cytotoxic edema and AQP4 expression was positively correlated, our results indicated that metformin may reduce the formation of cytotoxic edema. However, given that AQP4 plays a key role in the elimination of cerebral edema, attenuation of AQP4 expression by metformin may reduce the elimination of cerebral edema. Hence, future studies will be necessary to dissect the specific mechanisms of metformin underlying the dynamics of tumor-induced brain edema in vivo.

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This case report deals with multiple intracranial metastatic tumors and studies of expression and regulation characteristics of aquaporins (AQPs) of cerebellar metastatic tumor and brain tissue surrounding tumor. In this work, we try to understand the role of abnormal expression of AQPs in formation and elimination of brain edema and provide new ideas for the treatment of brain edema induced by tumor. The work involves resection of intracranial occupying lesions to get cerebellar metastatic tumor organization. Total RNA was extracted, RT-PCR was done, and immunohistochemical staining was done to study the expression and regulation characteristics of AQPs. We found that AQP4 had a high expression in the peritumoral brain tissue and no expression in the center of brain metastasis tumor organization. Around the tumor tissue, the AQP4 staining was junior in the more distant region from tumor and it added significantly in close to the tumor tissue region. It demonstrated that the AQP4 expression was upregulated, obviously with the distance drawing near gradually to tumor tissue. In addition, stained AQP1 was not observed on cerebellar metastatic tumor and peritumoral brain microvascular endothelial cells. The phenomenon that AQP4 had an increased expression in the surrounding region of cerebellar metastatic tumor and, moreover, increased significantly in the region next to the cerebellar metastatic tumor tightly is probably related to the formation of peritumoral brain edema and plays an important role in cytotoxic brain edema mechanism. AQP1 was not expressed on cerebellar metastatic tumor and peritumoral brain tissue microvascular endothelial cells, and this may be an important factor that the peritumoral interstitial brain edema is removed ineffectively to cause ‘small tumor, big edema.’

Experimental autoimmune neuritis ( EAN ), an animal model of human Guillain–Barré syndrome, has long been considered as a T helper (Th) 1 cell–mediated autoimmune disorder. However, deficiency of IFN ‐ γ , a signature Th1 cytokine, aggravated EAN , with features of elevated production of IL ‐17A, despite an alleviated systemic Th1 immune response. We hypothesized that Th17 cells and their cytokines might play a pathogenic role in EAN . To further clarify the roles of these Th and regulatory T cell (Treg) cytokines in the pathogenesis of EAN and their interrelationship, we investigated the expression of Th1/Th2/Th17/Treg cytokines in EAN in this study. We found that the levels of Th17 cells and IL ‐17A in cauda equina ( CE )‐infiltrating cells and splenic mononuclear cells ( MNC s) as well as in serum paralleled the disease evolution, which increased progressively during the initiation stage and reached higher value at the peak of EAN . The same pattern was also noticed for the expression of IL ‐22. The diverse expression profiles of FoxP3, IL ‐17 receptors A and C were seen in CE ‐infiltrating cells and splenic MNC s in EAN . These findings indicate a major pro‐inflammatory role of Th17 cells and IL ‐17A in the pathogenesis of EAN . Therapeutic interventions may be focused upon inhibiting Th17 cells and their cytokines in the early phase of EAN , so as to delay and suppress clinical signs of the disease, which has relevance for future studies on pathogenesis and treatment of GBS in humans.

Guillain–Barré syndrome (GBS) is an immune-mediated inflammatory disease in the peripheral nervous system. Specific biomarkers for the two most common clinical subtypes of GBS, i.e., acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) are still missing. The distinctive pathological features of AIDP and AMAN may lead to release of such specific biomarkers including glial markers (calcium-binding astroglial protein, S100B) and axonal damage markers [axoskeletal protein, phosphorylated neurofilament heavy protein (pNFH); cytoskeletal protein, tau], etc. To explore the potentials of biochemical markers for differential diagnosis and evaluation of prognosis of clinical subtypes in GBS, we used ELISA to measure the levels of S100B, tau and pNFH in serum and cerebrospinal fluid (CSF) from the patients with AIDP, AMAN, viral encephalitis and other non-inflammatory neurological disorders (OND), respectively. The values of albumin quotient and IgG index in CSF are significantly higher in AIDP and AMAN than in OND. The levels of S100B, tau and pNFH in serum and CSF are elevated in the patients with AIDP and AMAN compared to OND. The concentrations of these proteins are all higher in CSF than in serum. Increased levels of S100B in CSF at the acute phase are positively correlated with the GBS disability scale scores (GDSs) in AIDP, whereas enhanced levels of tau and pNFH in CSF are positively correlated with the GDSs in AMAN. Increased CSF levels of S100B, tau and pNFH at the acute phase may predict a poor prognosis and evaluate the severity of AIDP or AMAN at plateau and the recovery phase. Elevated levels of pNFH in CSF may be used for differentiating between AMAN and AIDP.

To the Editor Noda and colleagues described a case with reversible cerebral vasoconstriction syndrome (RCVS) and subarachnoid hemorrhage (SAH), as well as posterior reversible encephalopathy syndrome (PRES) and cerebral infarction (1). The case is interesting; however, we would argue against their hypothesized scenario with regard to the pathogenic course of the disease. In this case, SAH, localized in the right superior frontal lobe, was noted by computed tomography (CT) at the very early stage. Although digital subtraction angiography (DSA) on the same day demonstrated an unruptured aneurysm in the left internal carotid artery, no typical segmental vasoconstriction in the anterior or posterior circulation was identified. DSA performed later revealed multiple segments of irregularity consisting of narrowed areas of multiple branches of internal carotid arteries, indicative of RCVS. It is thus more plausible that RCVS and generalized seizures arise from SAH per se. The unruptured aneurysm, along with a history of hypertension, supports an aneurysmal etiology of SAH, despite the findings that a minimal amount of subarachnoid blood overlied the cortical surface and that the vasoconstriction was widespread. However, we cannot rule out the possibility that RCVS may in turn aggravate SAH manifestations. PRES was initially described by Hinchey et al (2) in 1996 as a clinico-radiological syndrome. Different conditions may attribute to the pathogenesis of PRES, including eclampsia, hypertensive encephalopathy, renal diseases and the use of immunosuppressive drugs (3). The pathophysiological mechanism of PRES is vasogenic edema (4), which requires apparent diffusion coefficient (ADC) maps elaborated from magnetic resonance diffusion-weighted imaging (DWI) for identification (5). Since an acknowledged set of diagnostic criteria for PRES is lacking, we are concerned about the diagnosis of PRES in this case. As discussed by the authors, some of the right parietooccipital hyperintense lesions on FLAIR images were hypointense, and the left frontal hyperintense lesion on FLAIR images was isointense on DWI, which are indicative of vasogenic edema. We are strongly against this assumption, because ADC maps are well acknowledged to be more sensitive and specific for vasogenic edema than DWI. In summary, the clinical course of the above-mentioned case can be explained by the scenario that hypertensionassociated SAH followed by vasospasm leads to RCVS and cerebral infarction.

Previous studies have shown that interferon-gamma (IFN-γ) is a proinflammatory cytokine that contributes to the pathogenesis of Guillain-Barré syndrome and its animal model, experimental autoimmune neuritis (EAN). Treatments with anti-IFN-γ antibodies improve clinical outcome in GBS patients and EAN animals and administration of IFN-γ markedly worsens EAN. Paradoxically, the mice deficient in IFN-γ remain susceptible to experimental autoimmune encephalomyelitis, an analogous disease in the central nervous system. These observations raise a question whether IFN-γ might be protective in autoimmune demyelinating diseases. To clarify the role of IFN-γ in the pathogenesis of autoimmune demyelinating diseases, we used P0 protein peptide 180-199 to induce EAN in IFN-γ knockout (KO) mice. After the acute phase of EAN, the clinical signs of IFN-γ KO mice were significantly more severe than those of wild type (WT) controls. After antigenic stimulation, the proliferation of splenic mononuclear cells was significantly higher in IFN-γ KO than in WT mice with EAN. At the peak of EAN, the proportion of interleukin (IL)-17A expressing cells in cauda equina (CE) infiltrating cells, and the levels of IL-17A in sera were elevated in IFN-γ KO mice when compared with their WT counterparts. The proportions of major histocompatibility complex (MHC) II, macrosialin, and IL-12/IL-23p40 expressing cells, relative to total CE infiltrating cells were correspondingly higher in IFN-γ KO than in WT mice with EAN. However, IFN-γ deficiency reduced the production of NO by cultured macrophages in response to proinflammatory stimuli and induced a systemic Th2-oriented immune response. In conclusion, IFN-γ deficiency exacerbates EAN via upregulating Th17 cells despite a mitigated systemic Th1 immune response.

Varaprasad and colleagues described a cohort of reversible encephalopathy in patients with systemic lupus erythematosus (SLE) 1 .This cohort adds to the increasing evidence that SLE can manifest reversible encephalopathy, e.g., posterior reversible encephalopathy syndrome (PRES) 2,3 .It is possible that PRES is underestimated in SLE.However, we are concerned about the differential diagnoses of these cases.PRES, also termed reversible posterior leukoencephalopathy syndrome, was initially described by Hinchey, et al 4 in 1996 as a clinico-radiological entity characterized by typical neurological deficits (headache, nausea and vomiting, altered mental status, visual impairment, and seizures), transient radiological brain anomalies, and a usually self-limited, benign and reversible clinical course.Different conditions might be attributable, such as eclampsia, hypertensive encephalopathy, renal diseases with hypertension, use of cyclosporine A or other immunosuppressive drugs 5,6 , etc.Other rare pathophysiological conditions, such as intracranial hypotension, have also been documented.The pathophysiological mechanism of PRES is suggested to be vasogenic edema, arising from failure of cerebrovascular autoregulation and disruption of the blood-brain barrier 7 .Although signal hyperintensity can be seen in magnetic resonance imaging (MRI), and T2-weighted imaging and fluid-attenuated inversion recovery images may show abnormal signal intensity, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps are indispensable to differentiate vasogenic edema in PRES from cytotoxic edema as well as ischemia 8 .Central nervous system (CNS) involvement in SLE is common.It can include vasculitis 9 , acute or subacute infarction 10 , and PRES 2,3 .Either lupus vasculitis or PRES may present with reversible lesions in the CNS.Therefore, reversible vasogenic edema as revealed by DWI and ADC maps, preferably involving the posterior white matter, can differentiate PRES from other reversible pathological changes in the CNS.For those patients with SLE who have neuropsychiatric manifestations, e.g., seizures, the reversible clinical symptoms and MRI anomalies may arise from epileptic seizures per se, rather than PRES.Since a well acknowledged set of diagnostic criteria for PRES is lacking, we wonder whether the authors considered other SLE-associated reversible lesions as the differential diagnoses.A failure to do so may lead to an overestimation of PRES in SLE.PRES does appear to be underestimated in SLE.However, the diagnosis of PRES might be confounded by other reversible pathological changes in SLE.