Astrocyte regulation of human brain capillary endothelial fibrinolysis

Kim, Jeong Ai; Tran, Nam; Wang, Shur-Jen; Fisher, Mark

doi:10.1016/j.thromres.2003.10.021

Cited by 31 publications

(23 citation statements)

References 52 publications

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“…Nevertheless, these findings are not indicative of a cAMPspecfic effect. Note that prior work has demonstrated that astrocytes enhance brain endothelial barrier properties concurrent with reduced tPA [3,4]; TGF-beta also induces similar findings [5]. Moreover, enhanced endothelial glut1 is consistent with upregulation of gamma glutamyl transpeptidase reported in prior similar work [3,4].…”

supporting

confidence: 78%

“…In an investigation of tPA expression in primate brain, capillary tPA expression was largely absent; capillaries comprised nearly 40% of all microvessels, yet more than 95% of capillaries showed no immunoreactivity for tPA [26]. Work from our laboratory showed astrocyte regulation of brain microvascular endothelial tPA expression [3,4]. Thrombomodulin, known to co-activate protein C with subsequent inhibition of PAI-1 [27], exhibited reduced expression in the current study, as was seen in prior work using astrocyte-endothelial co-cultures [22,5].…”

Section: Discussionmentioning

confidence: 99%

“…Reduced fibrinolytic capacity increases risk of thrombosis, and tPA as pharmacotherapy remains the only proven treatment of acute ischemic stroke [2]. Prior cell 632 culture investigation using brain microvascular endothelial cells and astrocytes has shown that endothelial tPA expression is negatively regulated by astrocytes [3,4]. Astrocyte regulation of tPA was inversely related to barrier properties of brain microvascular endothelial cells [3,4] and was mediated by TGF-beta [5].…”

Section: Introductionmentioning

confidence: 99%

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Tissue Plasminogen Activator Expression and Barrier Properties of Human Brain Microvascular Endothelial Cells

Yang¹,

Liu²,

Wang³

et al. 2011

Cell Physiol Biochem

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Background: Tissue plasminogen activator (tPA) regulates fibrinolysis and is routinely used as ischemic stroke pharmacotherapy. We hypothesized that brain microvascular tPA expression and barrier properties of endothelial cells are substantially related. Methods: Human brain microvascular endothelial cells were incubated with two agents known to modify cAMP pathways: forskolin and rolipram. We analyzed development of endothelial barrier properties, i.e., trans-endothelial electrical resistance (TEER), permeability of endothelial cell monolayer, expression of influx transporter glut-1 and endothelial tight junction molecules occludin and claudin-5, tPA antigen release, and levels of endothelial tPA mRNA. Results: Forskolin plus rolipram-treated endothelial cells showed increased TEER compared to controls (174±20% of control at day six, p<0.01), while permeability to albumin and 70kDa dextran was reduced (21±6.8% of control and 3.8±0.3% of control, respectively, p<0.001). In addition, occludin and claudin-5 protein were up-regulated, occludin mRNA was increased to 206±60% of control (p<0.05), glut-1 mRNA was increased to 196±68% of control (p<0.05), levels of tPA protein were reduced to 35±7.0% of control (p<0.001) after six days, and tPA mRNA was reduced to 32±7.7% of control (p<0.01). TPA and occludin mRNA levels were inversely associated (r=-0.68, p<0.05). Conclusions: In this in vitro model, barrier properties were strongly linked (by inverse association) with tPA expression of brain microvascular endothelial cells.

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supporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tissue Plasminogen Activator Expression and Barrier Properties of Human Brain Microvascular Endothelial Cells

Yang¹,

Liu²,

Wang³

et al. 2011

Cell Physiol Biochem

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“…Since both HBMEC and HA retain their BBB-specific properties at earlier passages, all the outlined experiments were performed using cells cultured up to and including passage 6 (Gu et al, 2003;Hurwitz et al, 1993;Kim et al, 2003).…”

Section: Cell Culturementioning

confidence: 99%

Inhibition of TNF-α protects in vitro brain barrier from ischaemic damage

Abdullah

Rakkar

Bath

et al. 2015

Molecular and Cellular Neuroscience

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The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.For more information, please contact eprints@nottingham.ac.uk activities while improving the barrier function through upregulation of tight junction protein expressions. In conclusion, vitiation of the exaggerated release of TNF-α may be an important therapeutic strategy in preserving cerebral integrity and function during and following a cerebral ischaemic attack.

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“…Recent studies have demonstrated that astrocytes can act as regulators of cerebral blood flow, various trophic factors, glutamate metabolism, potassium buffering and neuronal-glial signaling (Walz 1987(Walz , 1989Gallo et al 1996;Allan 2005;Kim et al 2003;Haberg et al 2006). Astrocytes also associate with synapses integrate neuronal inputs and release transmitters that modulate synaptic sensitivity (Hansson and Ronnback 2003).…”

Section: Introductionmentioning

confidence: 99%

Optimized and efficient preparation of astrocyte cultures from rat spinal cord

Yang

Liang

et al. 2006

Cytotechnology

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Astrocytes constitute a major class of glial cells in the CNS, and play crucial roles in physiological functioning, performance and maintenance of the CNS, as well as promotion of neuronal migration and maturation. Astrocytes have also been directly and indirectly implicated in the pathophysiology of various trauma occurrences, development of neurodegenerative diseases and nerve regeneration. To further understand mechanisms by which astrocytes elicit these effects, the first critical step in the study of astrocytes is the preparation of purified astrocytes cultures. Here we describe a simple and convenient procedure for producing rat primary astrocyte cultures of high purity, viability and proliferation. For astrocyte culture, we have optimized the isolation procedures and cultivation conditions including coating substrates, enzyme digestion, seeding density and composition of the culture medium. Using immunofluorescent antibodies against GFAP and OX-42 in combination of Hoechst 33342 fluorescent staining, we found that the purity of the astrocyte cultures was >99%. Astrocytes had high viability as measured by 3-(4, 5-dimethyl-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. In addition, flow cytometric analysis was used to measure and observe variations in the cell cycle after 1-2 passages and proliferation of astrocytes was detected with a high percentage of cells stand in S+G 2 /M phase. Therefore, the method described here is ideal for experiments, which require highly pure astrocyte cultures.

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Astrocyte regulation of human brain capillary endothelial fibrinolysis

Cited by 31 publications

References 52 publications

Tissue Plasminogen Activator Expression and Barrier Properties of Human Brain Microvascular Endothelial Cells

Tissue Plasminogen Activator Expression and Barrier Properties of Human Brain Microvascular Endothelial Cells

Inhibition of TNF-α protects in vitro brain barrier from ischaemic damage

Optimized and efficient preparation of astrocyte cultures from rat spinal cord

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