Effect of subventricular zone invasion on prognosis of glioma patients / 中国肿瘤临床

This work was supported by Science and Technology Program of Health and Family Planning Commission of Jiangxi Province (No.20161106) Abstract Objective: To investigate the prognostic value of subventricular zone (SVZ) invasion in glioma patients. Methods: The clini-cal data of 175 patients with glioma diagnosed based on pathology in Jiangxi Province Cancer hospital between January 2010 and July 2015 were analyzed retrospectively. There were 59 cases of World Health Organization (WHO) gradeⅡ, 59 cases of WHO gradeⅢ, and 57 cases of WHO gradeⅣat the first diagnosis. There were 75 cases of SVZ invasion (SVZ+) and 100 cases of SVZ non-invasion (SVZ-) according to preoperative magnetic resonance imaging. The survival outcomes of both cohorts were compared using the Log-rank test. The correlation between the recurrence pattern and SVZ involvement was analyzed using Chi-square tests. Results: The me-dian follow-up time was 63 months. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 42.2% and 37.5%, respectively. These were 20.9% and 15.3% in the SVZ+group, compared with 57.1% and 44.1% in the SVZ-group, respectively (P<0.001 and P<0.001, respectively). The SVZ+group had fewer cases of total resection, larger lesions (maximum diameter greater than 5.0 cm), and more cases of gradeⅣ(P<0.001, P<0.001, and P=0.018, respectively). There were 89 cases of recurrence. The total recur-rence rate was 62.7% in the SVZ+group, compared with 42.0% in the SVZ-group (P=0.007); the distant recurrence rates were 21.3% and 7.0% (P=0.004), respectively. Conclusions: SVZ invasion is a poor prognostic factor for OS and PFS in gliomas, which is positively correlated with a low total resection rate, large lesions, and gradeⅣlesions, and increases the probability of total recurrence and dis-tant recurrence.

Single-cell transcriptomics reveals gene signatures and alterations associated with aging in distinct neural stem/progenitor cell subpopulations

Aging associated cognitive decline has been linked to dampened neural stem/progenitor cells (NSC/NPCs) activities manifested by decreased proliferation, reduced propensity to produce neurons, and increased differentiation into astrocytes. While gene transcription changes objectively reveal molecular alterations of cells undergoing various biological processes, the search for molecular mechanisms underlying aging of NSC/NPCs has been confronted by the enormous heterogeneity in cellular compositions of the brain and the complex cellular microenvironment where NSC/NPCs reside. Moreover, brain NSC/NPCs themselves are not a homogenous population, making it even more difficult to uncover NSC/NPC sub-type specific aging mechanisms. Here, using both population-based and single cell transcriptome analyses of young and aged mouse forebrain ependymal and subependymal regions and comprehensive "big-data" processing, we report that NSC/NPCs reside in a rather inflammatory environment in aged brain, which likely contributes to the differentiation bias towards astrocytes versus neurons. Moreover, single cell transcriptome analyses revealed that different aged NSC/NPC subpopulations, while all have reduced cell proliferation, use different gene transcription programs to regulate age-dependent decline in cell cycle. Interestingly, changes in cell proliferation capacity are not influenced by inflammatory cytokines, but likely result from cell intrinsic mechanisms. The Erk/Mapk pathway appears to be critically involved in regulating age-dependent changes in the capacity for NSC/NPCs to undergo clonal expansion. Together this study is the first example of using population and single cell based transcriptome analyses to unveil the molecular interplay between different NSC/NPCs and their microenvironment in the context of the aging brain.

Advances in Adult Neurogenesis in Mammal Subventricular Zone / 现代生物医学进展

Neurogenesis is a process in which the neuronal stem cells differentiate into functional neurons including the cell proliferation,differentiation and migration.Previously,it was believed that neurogenesis is a prenatal process and the adult ependymal cells are incapable of regeneration.Now it is clear that mammalian brain retains the ability to generate new ceils in specific regions.One of the regions is subventricular zone of the lateral ventricles,new generated neurons and glial cells later migrate to olfactory and repair dysosmia through the RMS road.Here we will review the advances in adult neurogenesis in mammal subventficular zone.

Effect of total saponins of Panax notoginseng on neuroregeneration in subventricle zone of rats with global cerebral ischemia / 中草药

Objective: To explore the effect of total saponins of Panax notoginseng (TSPN) on the neuroregeneration in subventricle zone (SVZ) in rats with global cerebral ischemia. Methods: Using four-vessel occlusion method to build the global cerebral ischemia model. Rats were divided into Sham group, vehicle group, and TSPN group. The rats in TSPN group were ip administered with TSPN 30 min post-brain ischemia. The dose of TSPN (75 mg/kg) was suspended in 0.9% saline (10 g/L), once per day for 1, 3, 7, 14 days after reperfusion. While rats in the vehicle group were treated with equal volume of 0.9% saline, one injection per day until the rats were sacrificed at either 1, 3, 7, and 14 days after brain ischemia. The BrdU and Doublecortin (DCX) expression in SVZ was assessed by immunohistochemistry and applying the immunofluorescence double-labelling to detect the BrdU/DCX, DCX/Ki67, and GFAP/DCX in SVZ. Results: In comparison with the vehicle group, the number of BrdU+ cells in SVZ of TSPN group was significantly higher on days 7 and 14 (P < 0.01, 0.001); Statistical meaning existed in two groups on days 7 and 14 about the mean optical density of DCX+ cells in SVZ (P < 0.01, 0.001). In comparison with the vehicle group, the number of the BrdU-labeled cells co-expressing DCX in the SVZ on day 14t of TSPN group was significantly different (P < 0.01, 0.001). There was statistical meaning in comparison of the number of colocalization of DCX with Ki67 on days 7 and 14 in SVZ between the TSPN group and vehicle group (P < 0.01, 0.001). The ratio of GFAP/DCX to DCX in SVZ of two groups were statistically different on days 2, 7, and 14 (P < 0.05, 0.001). Conclusion: TSPN could promote the neuroregeneration, drive the proliferation and differentiation of neural progenitor cells, and enhance the differentiation of gliosis into newborn immature neurons in SVZ of rats with global cerebral ischemia.

Effects of Danlong XingnaoFormula on Proliferation of Neural Stem Cells in SVZ and Expressions of c-jun and c-myc in Cerebral Ischemia Reperfusion Rats / 中国中医药信息杂志

Objective To study the relationship of proliferation of neural stem cells (NSCs) in SVZ and the expressions of c-jun and c-myc in rats with middle cerebral artery occlusion/reperfusion (MCAO/R) injury model administrated byDanlong XingnaoFormula.Methods The focal cerebral ischemia reperfusion injury models were prepared by longa method. Totally 150 male SD rats were randomly divided into sham-operation group, cerebral model group,Danlong XingnaoFormula low-, medium-, and high-dose groups. The treatment groups were given corresponding dose ofDanlong XingnaoFormula, while the sham-operation group and model group were given the same amount of distilled water 24 h after modeling by gavage, once a day, 7 days in a row. 1 d, 3 d and 7 d after reperfusion, modified Neurological Severity Scores (m-NSS) was used to grade neurologic impairment. 7 d after reperfusion taken to the SVZ brain tissue of ischemia side, Brdu immunohistochemical method was used to record the BrdU positive cells number. The hippocampal c-jun, c-myc mRNA and protein expressions were determined respectively by RT-qPCR method and Western blot method.Results Grades of neurologic impairment in others groups were improved obviously than sham-operation group (P<0.01); 3 d, and 7 d after reperfusion, grades of neurologic impairment inDanlong XingnaoFormula groups were obviously lower compared with model group (P<0.05,P<0.01). Brdu positive cell rates in others groups increased obviously compared with sham-operation group; Compared with model group, Brdu positive cell rates inDanlong XingnaoFormula groups increased obviously (P<0.01). The expressions of c-jun and c-myc protein and mRNA inDanlong XingnaoFormula groups improved obviously than sham-operation group and model group (P<0.01).ConclusionDanlong Xingnao Formula can improve the neural function after cerebral ischemia and stimulate the proliferation of NSCs, and the mechanism may be related to activating the expression of c-jun and c-myc and extending the duration.

Acteoside promotes proliferation of neural stem cells from adult mice by activating PI3 K/AKT pathway / 中国药理学通报

Aim Toclarifytheeffectofacteosideon proliferation of neural stem cells (NSCs ) from adult mice,as well as the involved signaling pathway.Meth-ods NSCswereisolatedfromthesubventricularzone (SVZ)of adult C57BL/6 mice,then identified by im-munofluorescence staining with Nestin,the marker of NSCs.NSCs were exposed to acteoside (5,10,20,40μmol·L-1 )in absence of mitogen(EGF/bFGF)for 24 h.We employed CCK8 assay to detect NSCs viability and BrdU staining to identify NSCs proliferation.We performed Western blot to quantify the expression level ofp-AktinducedbyacteosideonNSCs.Results With-out mitogen,acteoside increased NSCs proliferation by activating p-Akt,which can be blocked by LY294002, the inhibitor of PI3K/AKT signaling pathway.Conclu-sion ActeosidepromotestheproliferationofNSCsfrom adult mice by activating PI3K/AKT pathway.

Effect of Ligustrazine on nNOS expression in different encephalic regions after focal cerebral ischemia in adult rats / 西安交通大学学报(医学版)

0.05).In SVZ,nNOS expression in ischemic model group was reduced on days 1-14,but increased on day 21;after Ligustrazine administration,nNOS expression was obviously decreased on days 3-14 in all Ligustrazine dose groups,but began to increase on day 21.In CC,nNOS expression in ischemic model group was reduced on days 3-14,and began to increase on day 21;in the different-dose Ligustrazine groups,nNOS expression was significantly decreased on days 3-14,especially in medium-and high-dose groups,but increased on day 21.In striatum and cortex peri-infarction,nNOS expression in ischemic model group was obviously decreased on days 3 and 7,but enhanced on days 14 and 21;in various-dose Ligustrazine groups,nNOS expression was decreased on days 3-21,especially in medium-and high-dose groups,but increased slightly on day 21.In DG and CA1 areas,nNOS expression in ischemic model group was reduced on days 3 and 7,but began to increase on day 14;nNOS expression in all Ligustrazine groups were decreased during 3-21d.There were significant differences between ischemic model group and different-dose Ligustrazine groups at different time points(P