Tanshinone IIA attenuates cerebral aneurysm formation by inhibiting the NF­κB­mediated inflammatory response.

The inflammatory response plays a vital role in cerebral aneurysm (CA) formation and progression. Tanshinone  IIA (Tan IIA) is one of the major active components of Chinese medicine Danshen (Salvia miltiorrhiza Bunge) and is widely used for the treatment of cardiovascular diseases, due to its anti­inflammatory effects. The aim of the present study was to investigate whether Tan IIA can attenuate CA formation in rat models, and determine its underlying mechanisms. CAs were induced in rats surgically and through high­salt diet treatments. The Tan IIA­treated group displayed relatively mild symptoms, as compared with the control group. Tan IIA treatment reduced macrophage infiltration and nuclear factor (NF)­κB activation in aneurysmal walls. Next, lipopolysaccharide (LPS)­stimulated RAW 264.7 murine macrophage cells were used to examine the anti­inflammatory effects of Tan IIA on macrophages. It was found that Tan IIA reversed LPS­induced differentiation of RAW 264.7 cells and suppressed NF­κB pathway activation. In conclusion, these findings demonstrated that Tan IIA can suppress CA formation by inhibiting inflammatory responses in macrophages.

Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature.

The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial fibrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identified using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromodeoxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial fibrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our findings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

Downregulation of VEGF expression attenuates malignant biological behavior of C6 glioma stem cells.

Several lines of direct evidence show that gliomas express high levels of vascular endothelial growth factor (VEGF). VEGF can promote the growth of gliomas through angiogenesis. It is believed that gliomas originate in the brain tumor stem cells (BTSCs). However, the direct effect of VEGF on the biological behavior of BTSCs has not been completely elucidated. In this study, we established C6 glioma stem cells (C6GSCs) from the C6 glioma cells. Furthermore, we suppressed the VEGF expression of C6GSCs using lentiviral vector-VEGF shRNA. After transfection, the VEGF expression of C6GSCs was downregulated significantly. The proliferation and invasion capacity of transfected C6GSCs was impaired and the ability of differentiation was enhanced. The data demonstrate that downregulation of VEGF expression attenuates malignant biological behavior of C6GSCs. RNA interference of VEGF expression implies an effective anti-gliomas strategy.

Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models.

Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc(+)/SV40Tag(+)/Tet-on(+)) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cells and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cells were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibrillary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibrillary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibrillary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cells. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells.