Animals ; Basilar Artery ; Brain Ischemia ; pathology ; Brain Stem ; blood supply ; Cats ; Medulla Oblongata ; blood supply

Age Factors ; Animals ; Animals, Newborn ; Blood-Brain Barrier ; Brain ; blood supply ; physiopathology ; Brain Ischemia ; physiopathology ; therapy ; Models, Animal ; Rats ; Stem Cell Transplantation

Anti-angiogenic therapy has shown promising but insufficient efficacy on gliomas. Recent studies suggest that vasculogenic mimicry (VM), or the formation of non-endothelial, tumor-cell-lined microvascular channels, occurs in aggressive tumors, including gliomas. There is also evidence of a physiological connection between the endothelial-lined vasculature and VM channels. Tumor cells, by virtue of their high plasticity, can form vessel-like structures themselves, which may function as blood supply networks. Our previous study on gliomas showed that microvessel density was comparably less in VM-positive tumors than in VM-negative tumors. Thus, VM may act as a complement to ensure tumor blood supply, especially in regions with less microvessel density. Patients with VM-positive gliomas survived a shorter period of time than did patients with VM-negative gliomas. Although the detailed molecular mechanisms for VM are not fully understood, glioma stem cells might play a key role, since they are involved in tumor tissue remodeling and contribute to neovascularization via transdifferentiation. In the future, successful treatment of gliomas should involve targeting both VM and angiogenesis. In this review, we summarize the progress and challenges of VM in gliomas.
Antigens, CD34 ; metabolism ; Brain Neoplasms ; blood supply ; pathology ; therapy ; Glioma ; blood supply ; pathology ; therapy ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Microcirculation ; Neoplasms ; blood supply ; pathology ; therapy ; Neoplastic Stem Cells ; pathology ; Neovascularization, Pathologic ; Prognosis

A 48-year-old hypertensive man had sudden onset of symptoms suggesting vertebrobasilar insufficiency, which were transient in nature lasted for only 4 hours. Brain computed tomography revealed a small hematoma in the pontomedullary junction. This is an uncommon presentation of benign brainstem hemorrhage simulating transient ischemic attack. We propose that computed tomographic scan using thin slices of 3mm to 5mm thickness at the level of brainstem is required before starting anticoagulation therapy for vertebrobasilar transient ischemic attack.
Brain Stem/*blood supply ; Cerebral Hemorrhage/*diagnosis ; Diagnosis, Differential ; Human ; Ischemic Attack, Transient/*diagnosis ; Male ; Middle Aged ; Tomography, X-Ray Computed

OBJECTIVETo investigate the effects of atrial natriuretic peptide (ANP) on ischemia and reperfusion cochlea in guinea pigs.

METHODSThe guinea pigs were randomly allocated into four groups: experiment groups (A1 and B1) and control groups (A2 and B2). Cochlear ischemia and reperfusion was induced by thrombus and thrombolysis method. In experiment group A1, ANP was administered 10 min before the ischemic insult. In experiment group B1, ANP was administered at the beginning of reperfusion. In control groups, instead of ANP, normal sodium was injected. The blood flow of cochlea (CoBF) was monitored continuously with laser Doppler flow meter and the threshold of auditory brainstem response (ABR) was measured.

RESULTSBefore the induction of ischemia, the CoBF of experiment group A1 was higher than that of the control group A2. From the reperfusion moment to the end of the experiment, there was no difference between the CoBF of the two groups. In B1 and B2 groups, no difference could be seen between the two groups before the induction of ischemia. After reperfusion, the blood flow of control group B2 recovered to 70% of the base level, while the CoBF of experiment group B1 restored to almost the same level of the beginning. Before ischemia, the ABR threshold of the four groups had no difference. At 30 min of ischemia, the threshold of experiment group Al was lower than that of control group A2. And there was no difference in experiment group B1 and control group B2. At 30 min and 60 min of reperfusion, the threshold of experiment group B1 was significantly lower than that of control group B2. No difference could be seen between experiment group A1 and control group A2.

CONCLUSIONSAdministration of ANP at the beginning of reperfusion protects the cochlea from ischemia and reperfusion injury. The administration can not only increase the CoBF, but lower the ABR threshold.

Animals ; Atrial Natriuretic Factor ; pharmacology ; Cochlea ; blood supply ; drug effects ; physiopathology ; Disease Models, Animal ; Evoked Potentials, Auditory, Brain Stem ; Guinea Pigs ; Reperfusion Injury ; drug therapy ; physiopathology

To evaluate the efficacy of magnetic resonance imaging in brainstem stroke, we studied 21 cases of clinically definite brainstem ischemic stroke with brain magnetic resonance imaging (MRI) and conventional computed tomography (CT). MRI demonstrated brainstem lesions in 79% of the cases (16.5 out of 21), while CT revealed 33% (7 out of 21) when cases with suspicious lesions counted as 0.5. Although MRI was done a few days later than CT in most cases, MRI was superior to CT in detecting the number and the size of ischemic lesions, with clear delineation of anatomy and visualization of the status of the blood flow in the vertebral-basilar artery. Disappearance of the flow signal void in the basilar artery can be an important clue in diagnosing occlusion or thrombus of the basilar artery. By delineating the extent and the location of the infarction, MRI findings allowed an interpretation of whether the ischemic vessel is a small basilar branch or a large vessel vertebral or basilar artery.
Adult ; Aged ; Brain Ischemia/complications/*diagnosis/radiography ; Brain Stem/blood supply/*pathology/radiography ; Cerebral Infarction/etiology/pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Tomography, X-Ray Computed

OBJECTIVEThe finding of vasculogenic mimicry (VM) in many solid tumors indicates that tumor cells themselves could participate in the construction of tumor vessels. However the origin of these cells is still not fully elucidated, and whether these vessels have the ability of blood-supply is still unclear. Preliminary studies were performed to investigate whether part of tumor neovascularity is derived from tumor stem cells (TSCs) and whether TSCs-derived vessels are functional.

METHODSTransplanted glioma tissues obtained from subcutaneous and orthotopic transplantation nude mouse models were processed into paraffin sections. In order to identify the cell origin and types of tumor vessels, sections were stained with CD31, CD34, CD133, GFAP, Ki67 and HLA, respectively. CD34-PAS staining was performed as well. A part of tumor-bearing mice were perfused with activated carbon through the systemic circulation and the distribution of activated carbon was observed.

RESULTSCD34-PAS staining showed that endothelium-dependent vessels (CD34(+), PAS(+)), VM vessels (CD34(-), PAS(+)), and the MVs (CD34(+), PAS(-)) could be seen in the transplantated tumors. Activated carbon particles were observed in all three types of vessels. CD31(+) cells adherent to the luminal surface of vessel wall. CD34(+) cells distributed along the vessels as well, but morphologically were more like a transition type between tumor cells and endothelial cells. Human specific Ki67 and HLA positive cells could be seen in the tumor vessels indicating that these vessels were derived from human tumor cells. Moreover, cells of tumor vessels were proved to be constructed by human tumor cells mainly and fusion cells of host cells and tumor cells under confocal microscope.

CONCLUSIONSThree types of blood supply sources including endothelium-dependent vessels, vasculogenic mimicry (VMs) and mosaic vessels (MVs) exist in transplantation tumors of human glioma. Glioma stem and progenitor cells (GSCPs) have the potential to differentiate and transdifferentiate into VMs and MVs.

AC133 Antigen ; Animals ; Antigens, CD ; metabolism ; Antigens, CD34 ; metabolism ; Brain ; blood supply ; Brain Neoplasms ; blood supply ; metabolism ; pathology ; Carbon ; metabolism ; pharmacokinetics ; Cell Line, Tumor ; Endothelium, Vascular ; metabolism ; pathology ; Glial Fibrillary Acidic Protein ; metabolism ; Glioma ; blood supply ; metabolism ; pathology ; Glycoproteins ; metabolism ; HLA Antigens ; metabolism ; Humans ; Ki-67 Antigen ; metabolism ; Mice ; Mice, Nude ; Microcirculation ; Neoplasm Transplantation ; Neoplastic Stem Cells ; metabolism ; pathology ; Neovascularization, Pathologic ; metabolism ; pathology ; Peptides ; metabolism ; Periodic Acid-Schiff Reaction ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism

Various stem cells, including neural stem cells (NSCs), have been extensively studied in stroke models, but how to increase neuronal differentiation rate of NSCs remains unresolved, particularly in a damaged environment. The purpose of this study was to investigate the effects of cerebral microvascular endothelial cells (CMECs) on the neurogenesis of NSCs with or without oxygen-glucose deprivation (OGD). The NSCs acquired from primary culture were immunostained to prove cell purity. Survival and proliferation of NSCs were determined after the co-culture with CMECs for 7 days. After removing the CMECs, NSCs were randomly divided into two groups as follows: OGD and non-OGD groups. Both groups were maintained in differentiation culture for 4 days to evaluate the differentiation rate. Mouse embryo fibroblast (MEF) cells co-cultured with NSCs served as control group. NSCs co-cultured with CMECs had an increase in size (on the 7th day: 89.80±26.12 μm vs. 73.08±15.01 μm, P<0.001) (n=12) and number [on the 7th day: 6.33±5.61/high power objective (HP) vs. 2.23±1.61/HP, P<0.001] (n=12) as compared with those co-cultured with MEF cells. After further differentiation culture for 4 days, NSCs co-cultured with CMECs had an increase in neuronal differentiation rate in OGD and non-OGD groups, but not in the control group (15.16% and 16.07% vs. 8.81%; both P<0.001) (n=6). This study provided evidence that OGD could not alter the effects of CMECs in promoting the neuronal differentiation potential of NSCs. These findings may have important implications for the development of new cell therapies for cerebral vascular diseases.
Animals ; Animals, Newborn ; Brain ; blood supply ; Cell Differentiation ; physiology ; Cell Proliferation ; Cells, Cultured ; Coculture Techniques ; methods ; Endothelial Cells ; cytology ; metabolism ; Glucose ; metabolism ; Mice ; Mice, Inbred C57BL ; Microvessels ; cytology ; metabolism ; Neural Stem Cells ; cytology ; metabolism ; Oxygen ; metabolism

OBJECTIVETo explore the method for labeling Flk1+ CD31- CD34- human bone marrow mesenchymal stem cells (hBMSCs) with ferumoxide-PLL and evaluate the feasibility of its tracing after transplantation into the brains of Macaca Fascicularis.

METHODSThe hBMSCs were incubated with ferumoxide-PLL. Trypan blue staining, Prussian blue staining, and transmission electron microscope were performed to show intracellular iron, marking efficiency, and the vigor of the labeled cells. After the hBMSCs were transplanted into the brains of cynomolgus monkeys by stereotaxis, magnetic resonance imaging (MRI) was performed to trace the cells in vivo. Cell survival and differentiation were studied with immunohistochemistry, Prussian blue staining, and HE staining.

RESULTSThe marking efficiency of the ferumoxide-PLL was 96%. Iron particles were found intracytoplasmic of the hBMSCs by Prussian blue staining and transmission electron microscopy. The relaxation rates of labeled cells in MRI were 4.4 and 4.2 times higher than those of the unlabeled cells. Hypointensity area was found by MRI three weeks after transplantation. Many hBMSCs and new vessels were found in the transplantation zone by pathological and immunofluorescence methods.

CONCLUSIONSFerumoxide-PLL can effectively label hBMSCs and thus increase its contrast in MRI results. The cells can survive in the brains of cynomolgus monkeys. The labeled hBMSCs can be traced in vivo by MRI.

Animals ; Antigens, CD34 ; analysis ; metabolism ; Bone Marrow Cells ; chemistry ; metabolism ; Bone Marrow Transplantation ; Brain ; blood supply ; metabolism ; Brain Chemistry ; Contrast Media ; chemistry ; Dextrans ; Ferrosoferric Oxide ; chemistry ; Humans ; Macaca fascicularis ; Magnetic Resonance Imaging ; methods ; Magnetite Nanoparticles ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; chemistry ; metabolism ; Platelet Endothelial Cell Adhesion Molecule-1 ; analysis ; metabolism ; Staining and Labeling ; methods ; Vascular Endothelial Growth Factor Receptor-2 ; analysis ; metabolism

OBJECTIVETo isolate, culture and identify glioma stem cells from human malignant glioma cell line U87, and investigate the changes of pro-angiogenic factors production by glioma stem cells followed by activation of CXCR4 and observe their tumorigenesis as well as the expression of vascular endothelial growth factor when implanted into nude mice.

METHODSThe ratio of CD133 positive cells was detected by flow cytometry. Magnetic separation of CD133 positive cells was carried out on the magnetic cell sorting system (MACS). Expression of nestin, glial fibrillary acidic protein (GFAP) and CXCR4 on tumorspheres was detected by indirect immunofluorescence under confocal laser scanning microscopy. The functional activation of CXCR4 was assessed by calcium mobilization experiments. ELISA was used to detect the production of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in conditioned medium. Glioma stem cells were implanted into nude mice to assess their tumorigenesis ability and the expression of VEGF.

RESULTSThe ratio of CD133 positive cells with stem cell property was 0.5% in U87 cells. Activation of CXCR4 on glioma stem cells induced calcium mobilization and increased VEGF and IL-8 protein secretion. CD133 positive cells secreted more VEGF and IL-8 than their negative counterparts in vitro. Tumors derived from CD133 positive cells grew more rapidly and expressed elevated level of VEGF than their negative counterparts.

CONCLUSIONSThere are a small fraction of glioma stem cells in human glioblastoma cell line U87. Expressing functional CXCR4 and secreting more pro-angiogenic factors may be involved in tumor angiogenesis mediated by glioma stem cells.

AC133 Antigen ; Animals ; Antigens, CD ; analysis ; Brain Neoplasms ; blood supply ; metabolism ; pathology ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Glial Fibrillary Acidic Protein ; metabolism ; Glioblastoma ; blood supply ; metabolism ; pathology ; Glycoproteins ; analysis ; Humans ; Interleukin-8 ; metabolism ; Intermediate Filament Proteins ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Neoplastic Stem Cells ; metabolism ; transplantation ; Neovascularization, Pathologic ; Nerve Tissue Proteins ; metabolism ; Nestin ; Peptides ; analysis ; Receptors, CXCR4 ; genetics ; metabolism ; physiology ; Vascular Endothelial Growth Factor A ; metabolism