Galectin-3 modulates postnatal subventricular zone gliogenesis

Postnatal subventricular zone (SVZ) neural stem cells generate forebrain glia, namely astrocytes and oligodendrocytes. The cues necessary for this process are unclear, despite this phase of brain development being pivotal in forebrain gliogenesis. Galectin-3 (Gal-3) is increased in multiple brain pathologies and thereby regulates astrocyte proliferation and inflammation in injury. To study the function of Gal-3 in inflammation and gliogenesis, we carried out functional studies in mouse. We overexpressed Gal-3 with electroporation and using immunohistochemistry surprisingly found no inflammation in the healthy postnatal SVZ. This allowed investigation of inflammation-independent effects of Gal-3 on gliogenesis. Loss of Gal-3 function via knockdown or conditional knockout reduced gliogenesis, whereas Gal-3 overexpression increased it. Gal-3 overexpression also increased the percentage of striatal astrocytes generated by the SVZ but decreased the percentage of oligodendrocytes. These novel findings were further elaborated with multiple analyses demonstrating that Gal-3 binds to the bone morphogenetic protein receptor one alpha (BMPR1α) and increases bone morphogenetic protein (BMP) signaling. Conditional knockout of BMPR1α abolished the effect of Gal-3 overexpression on gliogenesis. Gain-of-function of Gal-3 is relevant in pathological conditions involving the human forebrain, which is particularly vulnerable to hypoxia/ischemia during perinatal gliogenesis. Hypoxic/ischemic injury induces astrogliosis, inflammation and cell death. We show that Gal-3 immunoreactivity was increased in the perinatal human SVZ and striatum after hypoxia/ischemia. Our findings thus show a novel inflammation-independent function for Gal-3; it is necessary for gliogenesis and when increased in expression can induce astrogenesis via BMP signaling.     

High throughput sequencing reveals high specificity of TNFAIP3 mutations in ocular adnexal marginal zone B-cell lymphomas

The majority of ocular adnexal (OA) lymphomas (OAL) are extranodal marginal zone lymphomas (MZL). First high throughput sequencing (HTS) studies on OA-MZL showed inconsistent results and the distribution of mutations in reactive lymphoid lesions of this anatomic region has not yet been sufficiently addressed. We characterized OAL and lymphoid lesions of the OA by targeted HTS. The study included 34 OA-MZL, 11 chronic conjunctivitis, five mature small cell B-cell lymphomas spreading to the OA, five diseases with increase of IgG4+ plasma cells, three Burkitt lymphomas (BL), three diffuse large B-cell lymphomas (DLBCL), three mantle cell lymphomas, three idiopathic orbital inflammations/orbital pseudo tumors (PT), and three OA lymphoid hyperplasia. All cases were negative for Chlamydia. The mutational number was highest in BL and lowest in PT. The most commonly (and exclusively) mutated gene in OA-MZL was TNFAIP3 (10 of 34 cases). Altogether, 20 out of 34 patients harbored mutually exclusive mutations of either TNFAIP3, BCL10, MYD88, ATM, BRAF, or NFKBIE, or nonexclusive mutations of IRF8, TNFRSF14, KLHL6, and TBL1XR1, all encoding for NK-κB pathway compounds or regulators. Thirteen patients (38%) had, to a great part, mutually exclusive mutations of chromatin modifier-encoding genes: KMT2D, CREBBP, BCL7A, DNMT3A, EP300, or HIST1H1E. Only four patients harbored co-occurring mutations of genes encoding for NK-κB compounds and chromatin modifiers. Finally, PTEN, KMT2D, PRDM1, and HIST1H2BK mutations were observable in reactive lymphoid lesions too, while such instances were devoid of NF-κB compound mutations and/or mutations of acetyltransferase-encoding genes. In conclusion, 80% of OA-MZL display mutations of either NK-κB compounds or chromatin modifiers. Lymphoid lesions of the OA bearing NF-κB compound mutations and/or mutations of acetyltransferase-encoding genes highly likely represent lymphomas.     

Confirmation of Two Magnetoencephalographic Epileptic Foci by Invasive Monitoring from Subdural Electrodes in an Adolescent with Right Frontocentral Epilepsy

PURPOSE: To report our evaluation of interictal two epileptic spike fields on magnetoencephalography (MEG) by using invasive intracranial monitoring in a patient without lesion on magnetic resonance imaging (MRI). METHODS: A 15-year-old left-handed boy with a 9-year history of refractory simple partial seizures, secondarily generalized, and a normal MRI, was studied with MEG to define magnetic spike sources, followed by invasive intracranial monitoring with subdural electrodes to delineate the epileptogenic zone and eloquent function pursuant to focal cortical excision. RESULTS: MEG demonstrated two spike foci on the right middle frontal and inferior rolandic areas adjacent to the sensory area. Ictal recordings during prolonged invasive monitoring from subdural electrodes revealed two epileptogenic zones in the same locations as those defined by MEG. Focal cortical excision was performed of each epileptogenic zone. The patient has been seizure free for 24 months without neurologic deficit. CONCLUSIONS: Magnetic source imaging is a valuable adjunct in the planning of subdural grid placement in epilepsy surgery, particularly in patients in whom conventional imaging fails to reveal a lesion.     

γ‐Aminobutyric acid‐ρ expression in ependymal glial cells of the mouse cerebellum

The ependymal glial cells (EGCs) from the periventricular zone of the cerebellum were studied to determine their distribution and the functional properties of their γ‐aminobutyric acid type A (GABA_A) receptors. EGCs were identified by the presence of ciliated structures on their ventricular surface and their expression of glial fibrillary acidic protein (GFAP). Interestingly, diverse cell types, including neurons, astrocytes, and other types of glia, were identified in the subventricular zone by their current profiles. Electron microscopy showed ciliated cells and myelinated axons in this zone, but we found no collateral connections to suggest the presence of functional synapses. GABA‐mediated currents were recorded from EGCs in cerebellar slices from postnatal days 13 to 35 (PN13–PN35). These currents were blocked by TPMPA (a highly specific GABA_Aρ subunit antagonist) and bicuculline (a selective antagonist for classic GABA_A receptors). Pentobarbital failed to modulate GABA_A‐mediated currents despite the expression of GABAα1 and GABAγ2 subunits. In situ hybridization, RT‐PCR, and immunofluorescence studies confirmed GABAρ1 expression in EGCs of the cerebellum. We conclude that cerebellar EGCs express GABAρ1, which is functionally involved in GABA_A receptor‐mediated responses that are unique among glial cells of the brain. © 2013 Wiley Periodicals, Inc.     

微血管减压术治疗神经源性高血压的研究

目的：探讨神经源性高血压的病因及外科治疗方法。方法：选择手术治疗的679例脑神经疾病病人为研究对象,将其分为左侧、右侧二大组。包括三叉神经痛590例,面肌痉挛74例,舌咽神经痛15例,其中89例病人术前有神经源性高血压。在行脑神经显微血管减压术（microvasculardecompression,MVD）的同时,探查同侧的延髓Ⅸ、Ⅹ脑神经人脑子区（rootentryzone,REZ）,有血管压迫者,将血管与该区的关系分为附着、压迫、粘连及贯穿型。术中74例行血管减压。结果：左侧组对高血压的治疗有效率为95．3％,右侧组为35．5％。结论：延髓左侧REZ受血管压迫是神经源性高血压的主要病因,行该区血管减压是治疗神经源性高血压的有效手段。     

经直肠超声检查和前列腺移行区特异抗原密度在前列腺癌穿刺活检中的作用

目的分析经直肠超声(TRUS)和前列腺移行区特异抗原密度(PSA-TZ)在前列腺癌穿刺活检中的作用,探讨个体化经直肠前列腺穿刺方案的可行性。方法依据TRUS结合PSA-TZ选择穿刺点,对64例可疑前列腺癌(PCA)患者,行经直肠前列腺穿刺活检。结果45例PSA-TZ≥0.35ng/ml.cm3,穿刺病理阳性41例,前列腺癌的检出率为91.1%,其中TRUS发现可疑病灶(TRUS+)35例均证实为癌。19例PSA-TZ<0.35ng/ml.cm3,穿刺病理阳性3例,前列腺癌的检出率15.8%,TRUS(+)5例,其中2例证实为癌。此两组患者前列腺癌的检出率差异显著(P<0.01)。结论当PSA-TZ≥0.35ng/ml.cm3,同时TRUS发现可疑病灶,建议行病灶穿刺;当PSA-TZ≥0.35ng/ml.cm3而TRUS阴性,宜行10点穿刺;若PSA-TZ<0.35ng/ml.cm3,TRUS阳性,则行包括病灶在内的6点穿刺。     

低强度脉冲超声在骨-肌腱结合部纤维软骨带修复中的作用

目的 研究低强度脉冲超声(LIPUS)对兔髌骨-髌腱结合部(BTJ)愈合的影响.方法 建立兔部分髌骨切除模型,超声组在术后3天开始为期6周的LIPUS治疗;对照组在术后不给予治疗;通过组织学染色观察BTJ纤维软骨移行带的修复,并进行生物力学测试,以评估其疗效.结果 ①组织学结果显示,超声组术后6周在截骨界面有大量新骨生成,BTJ可见大量新生软骨细胞;术后12周纤维软骨带初步形成;术后18周可见具有过渡结构的纤维软骨带.而对照组术后6周纤维母细胞增生,无新骨形成;术后18周出现大量新生软骨细胞,但缺乏纤维软骨带的过渡结构.②术后6、12和18周的力学测量结果显示,各组BTJ随时间的推移而逐渐改建,三个时间点超声组的极限拉应力均明显高于对照组(P＜0.05).结论 LIPUS可使骨、软骨等多种细胞增生,通过促进新骨形成及重建纤维软骨带而加快骨肌腱结合部位的早期恢复.     

毛细管区带电泳法测定三七药材中的三七素

目的测定三七中三七素的含量。方法采用毛细管区带电泳定量;用未涂层石英玻璃毛细管(65 cm×50μm,有效长度50 cm),检测波长200 nm,电压进样10 kV×5 s,运行电压30 kV,温度25℃,背景电解质为50 mmol·L-1NaH2PO4溶液(用0.1 mol·L-1氢氧化钠液调pH2.5)。结果方法的平均回收率为98.6%,RSD=2.3%(n=9)。结论所用方法简便快捷、灵敏度高、重复性好。