Brain derived neurotrophic factor does not act on adult human cerebral endothelial cells

Ruprecht, Klemens; Stadelmann, Christine; Hummel, Vera; Klein, Oliver; Brück, Wolfgang; Rieckmann, Peter

doi:10.1016/s0304-3940(02)00778-4

Cited by 7 publications

(5 citation statements)

References 18 publications

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“…Neurotrophins (BDNF) have been shown to be expressed by some, but not all, endothelial cells in culture (6,8,43). Using brain-derived, immortalized endothelial cells (RBE4 cells) we determined that these cells indeed express BDNF in our threedimensional culture system and that expression is increased following hypoxic treatment (Fig.…”

Section: Discussionmentioning

confidence: 99%

Paracrine and Autocrine Functions of Brain-derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in Brain-derived Endothelial Cells

Kim

Hempstead

et al. 2004

Journal of Biological Chemistry

193

146

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Brain-derived neurotrophic factor (BDNF) is expressed by endothelial cells. We investigated the characteristics of BDNF expression by brain-derived endothelial cells and tested the hypothesis that BDNF serves paracrine and autocrine functions affecting the vasculature of the central nervous system. In addition to expressing TrkB and p75 NTR and BDNF under normoxic conditions, these cells increased their expression of BDNF under hypoxia. While the expression of TrkB is unaffected by hypoxia, TrkB exhibits a base-line phosphorylation under normoxic conditions and an increased phosphorylation when BDNF is added. TrkB phosphorylation is decreased when endogenous BDNF is sequestered by soluble TrkB. Exogenous BDNF elicits robust angiogenesis and survival in three-dimensional cultures of these endothelial cells, while sequestration of endogenous BDNF caused significant apoptosis. The effects of BDNF engagement of TrkB appears to be mediated via the phosphatidylinositol (PI) 3-kinase-Akt pathway. Modulation of BDNF levels directly correlate with Akt phosphorylation and inhibitors of PI 3-kinase abrogate the BDNF responses. BDNF-mediated effects on endothelial cell survival/apoptosis correlated directly with activation of caspase 3. These endothelial cells also express p75 NTR and respond to its preferred ligand, pro-nerve growth factor (pro-NGF), by undergoing apoptosis. These data support a role for neurotrophins signaling in the dynamic maintenance/differentiation of central nervous system endothelia.Angiogenesis is a tightly controlled process in which new vessels form from those pre-existing. This process occurs in a regulated fashion during development and growth as well as in response to physiological and pathological stimuli. Angiogenesis as been shown to be a receptor-and ligand-regulated process, with a still growing, diverse number of soluble factors and their cognate receptors being involved in the different phases of the angiogenic process (1). In the developing brain, angiogenesis has been shown to be regulated by factors secreted by neuronal and glial cell populations in an orderly, spatiotemporal fashion (2). In recent studies we and others have (3,4) shown that selected angiogenic factors, VEGF 1 in particular, are capable of not only affecting a variety of endothelial behaviors but also are capable of affecting neuronal behavior in a receptor-specific fashion. Interestingly, recent studies have demonstrated that neurotrophins expressed by endothelia and are capable of influencing several endothelial cell functions including endothelial cell survival and vessel stabilization (5-7)

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Section: Discussionmentioning

confidence: 99%

Paracrine and Autocrine Functions of Brain-derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in Brain-derived Endothelial Cells

Kim

Hempstead

et al. 2004

Journal of Biological Chemistry

193

146

View full text Add to dashboard Cite

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“…TrkB receptor protein was detected in cultured rat CEC, 6 while TrkB mRNA was not found in human CEC collected from neurosurgical preparations. 98 We recently detected TrkB-FL and TrkB-T receptors in rat cerebral microvessels-enriched fractions. 93 Rodent astrocytes express TrkB, but only the TrkB-T1 isoform.…”

Section: Fate Of Bdnf Secreted By the Brain Endotheliummentioning

confidence: 96%

Brain-derived neurotrophic factor secreted by the cerebral endothelium: A new actor of brain function?

Marie

Pedard

Quirié

et al. 2018

J Cereb Blood Flow Metab

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Low cerebral levels of brain-derived neurotrophic factor (BDNF), which plays a critical role in many brain functions, have been implicated in neurodegenerative, neurological and psychiatric diseases. Thus, increasing BDNF levels in the brain is considered an attractive possibility for the prevention/treatment of various brain diseases. To date, BDNF-based therapies have largely focused on neurons. However, given the cross-talk between endothelial cells and neurons and recent evidence that BDNF expressed by the cerebral endothelium largely accounts for BDNF levels present in the brain, it is likely that BDNF-based therapies would be most effective if they also targeted the cerebral endothelium. In this review, we summarize the available knowledge about the biology and actions of BDNF derived from endothelial cells of the cerebral microvasculature and we emphasize the remaining gaps and shortcomings.

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“…Moreover, NGF interferes with monocyte migration through BBB‐ECs in vitro [125] and increases brain capillary ECs proliferation [123]. In one study, BDNF administration attenuated blood‐spinal cord barrier permeability in a spinal cord injury model [126], although this effect was not seen in a previous study [127]. GDNF, another neurotrophic factor, has been shown to enhance the BBB properties of brain capillary ECs in vitro [121].…”

Section: Direct Influence Of Immune Cells On the Bbbmentioning

confidence: 99%

How do immune cells overcome the blood–brain barrier in multiple sclerosis?

2011

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Keywords:Blood-brain barrier Multiple Sclerosis Leukocyte Cytokine Reactive oxygen species Matrix metalloproteinase a b s t r a c tThe presence of the blood-brain barrier (BBB) restricts the movement of soluble mediators and leukocytes from the periphery to the central nervous system (CNS). Leukocyte entry into the CNS is nonetheless an early event in multiple sclerosis (MS), an inflammatory disorder of the CNS. Whether BBB dysfunction precedes immune cell infiltration or is the consequence of perivascular leukocyte accumulation remains enigmatic, but leukocyte migration modifies BBB permeability. Immune cells of MS subjects express inflammatory cytokines, reactive oxygen species (ROS) and enzymes that can facilitate their migration to the CNS by influencing BBB function, either directly or indirectly. In this review, we describe how immune cells from the peripheral blood overcome the BBB and promote CNS inflammation in MS through BBB disruption.

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Brain derived neurotrophic factor does not act on adult human cerebral endothelial cells

Cited by 7 publications

References 18 publications

Paracrine and Autocrine Functions of Brain-derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in Brain-derived Endothelial Cells

Paracrine and Autocrine Functions of Brain-derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in Brain-derived Endothelial Cells

Brain-derived neurotrophic factor secreted by the cerebral endothelium: A new actor of brain function?

How do immune cells overcome the blood–brain barrier in multiple sclerosis?

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