Initial Contact of Glioblastoma Cells with Existing Normal Brain Endothelial Cells Strengthen the Barrier Function via Fibroblast Growth Factor 2 Secretion: A New In Vitro Blood–Brain Barrier Model

Toyoda, Keisuke; Tanaka, Kunihiko; Nakagawa, Shinsuke; Duong, Thuy; Ujifuku, Kenta; Kamada, Kensaku; Hayashi, Kentarō; Matsuo, Takayuki; Nagata, Izumi; Níwa, Masami

doi:10.1007/s10571-013-9913-z

Cited by 42 publications

(30 citation statements)

References 42 publications

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“…bFGF is demonstrated to preserve blood-brain barrier (BBB) integrity through RhoA inhibition after intracerebral hemorrhage in mice [23]. Moreover, in the in vitro BBB model, initial contact of glioblastoma cells with normal brain endothelial cells strengthens the barrier function via bFGF secretion, and a neutralization antibody for bFGF inhibits the recovery of BBB function [37]. Our previous reports show that bFGF treatment improves functional recovery after SCI, in part by inhibiting the apoptosis of neurons by inhibiting excessive autophagy and endoplasmic reticulum stress [21,22].…”

Section: Interaction Of Cav-1 and Fgfr1 Is Essential For The Functionmentioning

confidence: 99%

Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood–Spinal Cord Barrier and Functional Recovery

Xia

et al. 2016

Neurotherapeutics

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The blood-spinal cord barrier (BSCB) plays important roles in the recovery of spinal cord injury (SCI), and caveolin-1 is essential for the integrity and permeability of barriers. Basic fibroblast growth factor (bFGF) is an important neuroprotective protein and contributes to the survival of neuronal cells. This study was designed to investigate whether bFGF is beneficial for the maintenance of junction proteins and the integrity of the BSCB to identify the relations with caveolin-1 regulation. We examined the integrity of the BSCB with Evans blue dye and fluorescein isothiocyanate-dextran extravasation, measured the junction proteins and matrix metalloproteinases, and evaluated the locomotor function recovery. Our data indicated that bFGF treatment improved the recovery of BSCB and functional locomotion in contusive SCI model rats, reduced the expression and activation of matrix metalloproteinase-9, and increased the expressions of caveolin-1 and junction proteins, including occludin, claudin-5, p120-catenin, and β-catenin. In the brain, in microvascular endothelial cells, bFGF treatment increased the levels of junction proteins, caveolin-1 small interfering RNA abolished the protective effect of bFGF under oxygen-glucose deprivation conditions, and the expression of fibroblast growth factor receptor 1 and co-localization with caveolin-1 decreased significantly, which could not be reversed by bFGF treatment. These findings provide a novel mechanism underlying the beneficial effects of bFGF on the BSCB and recovery of SCI, especially the regulation of caveolin-1.

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Section: Interaction Of Cav-1 and Fgfr1 Is Essential For The Functionmentioning

confidence: 99%

Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood–Spinal Cord Barrier and Functional Recovery

Xia

et al. 2016

Neurotherapeutics

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“…There is evidence proving the benefit of FGF-2 in the blood–brain barrier (BBB) integrity [38,39] and in helping cell survival under oxidative stress by attenuating endoplasmic reticulum stress and mitochondrial injury. [40,41] In addition, MDD is believed to be a neurodegenerative disease with a possible etiology of inflammation and increased oxidative stress, [4,42] which may induce BBB dysfunction and cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Significantly higher peripheral fibroblast growth factor-2 levels in patients with major depressive disorder

Wu¹,

Tseng²,

Chen

et al. 2016

Medicine

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“…For example, upregulation of tight junction protein expression has been reported for Sonic Hedgehog, FGF-2, and GDNF [26–29]. Decreased BBB permeability has been reported in response to Sonic Hedgehog, Ang-1, FGF-2 and GDNF [26–27,29–30]. APoE4 plays a critical role in maintaining BBB integrity [31], and pericyte deficiency has been shown to increase vesicular transcytosis in brain ECs [32].…”

Section: Anatomy and Physiology Of The Blood–brain Barriermentioning

confidence: 99%

Promising Approaches to Circumvent the Blood–Brain Barrier: Progress, Pitfalls and Clinical Prospects in Brain Cancer

Papademetriou

Porter

2015

Ther. Deliv.

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Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood–brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers noninvasive delivery of small molecule and biological cancer therapeutics. Local delivery methods enable high dose delivery while avoiding systemic exposure. BBB disruption with focused ultrasound and microbubbles offers local and noninvasive treatment. Clinical trials show the prospects of these technologies and point to challenges for the future.

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Initial Contact of Glioblastoma Cells with Existing Normal Brain Endothelial Cells Strengthen the Barrier Function via Fibroblast Growth Factor 2 Secretion: A New In Vitro Blood–Brain Barrier Model

Cited by 42 publications

References 42 publications

Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood–Spinal Cord Barrier and Functional Recovery

Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood–Spinal Cord Barrier and Functional Recovery

Significantly higher peripheral fibroblast growth factor-2 levels in patients with major depressive disorder

Promising Approaches to Circumvent the Blood–Brain Barrier: Progress, Pitfalls and Clinical Prospects in Brain Cancer

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