2010
DOI: 10.1186/1742-2094-7-89
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Microglial activation state exerts a biphasic influence on brain endothelial cell proliferation by regulating the balance of TNF and TGF-β1

Abstract: BackgroundStudies of cerebral ischemia and other neuroinflammatory states have demonstrated a strong association between new vessel formation and microglial recruitment and activation, raising the possibility that microglia may be involved in promoting angiogenesis. As endothelial cell proliferation is a fundamental early step in angiogenesis, the aim of this study was to test this hypothesis by examining the influence of microglial secreted factors on brain endothelial cell (BEC) proliferation using BrdU inco… Show more

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Cited by 70 publications
(55 citation statements)
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“…In light of our current findings, showing similar upregulation of endothelial α5 integrin on remodeling cerebral blood vessels during the early stages of EAE, we next examined in vitro whether α5 integrin mediates the BEC proliferative response to a pro-inflammatory stimulus. Previously, we found that TNF-α strongly stimulates BEC proliferation (Welser et al 2010), and our current experiments, using bromodeoxyuridine (BrdU) incorporation, confirmed this finding, with TNF-α increasing proliferation (from 20.7 ± 1.8% under control conditions to 43.3 ± 2.9%, p < 0.001; see Figure 7D). Furthermore, incubation with an α5 integrin function-blocking antibody significantly reduced brain endothelial cell proliferation, both under non-stimulated conditions (from 20.7 ± 1.8% to 16.3 ± 2.1%, p < 0.05) and in response to TNF-α (from 43.3 ± 2.9% to 22.5 ± 4.6%, p < 0.005).…”
Section: Resultssupporting
confidence: 88%
“…In light of our current findings, showing similar upregulation of endothelial α5 integrin on remodeling cerebral blood vessels during the early stages of EAE, we next examined in vitro whether α5 integrin mediates the BEC proliferative response to a pro-inflammatory stimulus. Previously, we found that TNF-α strongly stimulates BEC proliferation (Welser et al 2010), and our current experiments, using bromodeoxyuridine (BrdU) incorporation, confirmed this finding, with TNF-α increasing proliferation (from 20.7 ± 1.8% under control conditions to 43.3 ± 2.9%, p < 0.001; see Figure 7D). Furthermore, incubation with an α5 integrin function-blocking antibody significantly reduced brain endothelial cell proliferation, both under non-stimulated conditions (from 20.7 ± 1.8% to 16.3 ± 2.1%, p < 0.05) and in response to TNF-α (from 43.3 ± 2.9% to 22.5 ± 4.6%, p < 0.005).…”
Section: Resultssupporting
confidence: 88%
“…296 The M2 phenotype microglia, in contrast, enhance BBB integrity by increasing TJ expression after stroke. 297 …”
Section: Part II Neurovascular Injury and Repair After Ischemic Strokementioning
confidence: 99%
“…During this period, microglia not only have key functions such as the clearance of dying or dead cells. Several studies are emerging that demonstrate a role in developmental processes such as apoptosis, elimination of excess axons, promotion of neuroaxonal growth, axonal guidance, neuronal differentiation, regulation of embryonic cortical precursor cell development, astrocyte proliferation and angiogenesis [20,30,34,35,36,37,38,39,40,41,42,43,44,45]. Especially the role of microglia in neurogenesis is intriguing as, within the framework of CNS inflammation, the impact of this feature on the developing brain can be enormous.…”
Section: Microglia In the Developing Brainmentioning
confidence: 99%