Vascular endothelial growth factor: Direct neuroprotective effect in
            <i>in vitro</i>
            ischemia

Jin, Kui; Mao, Xiao Ou; Greenberg, David A.

doi:10.1073/pnas.97.18.10242

Cited by 631 publications

(456 citation statements)

References 51 publications

(47 reference statements)

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“…Previous studies showed that hypoxia induces VEGF expression in various kinds of cells [2,10,14,15,17]. Kleiner et al [12] found increased collagen metabolic activities of the graft tissue 7 to 21 days after ACL reconstruction in the rabbit model.…”

Section: Discussionmentioning

confidence: 98%

Expression of vascular endothelial growth factor and angiogenesis in patellar tendon grafts in the early phase after anterior cruciate ligament reconstruction

Yoshikawa

Tohyama

Enomoto

et al. 2006

Knee Surg Sports Traumatol Arthr

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The aim of this study was to clarify vascular endothelial growth factor (VEGF) expression and angiogenesis in the patellar tendon autograft in the early phase after ACL reconstruction using a rabbit model. The right knees of 30 Japanese white rabbits underwent ACL reconstruction using the medial third of the patellar tendon complex. We evaluated the grafted tendon at 1, 2, 3, 4, and 8 weeks after ACL reconstruction by immunohistology for proliferating cell nuclear antigen (PCNA), VEGF, and CD31, which is a marker for vascular endothelial cells. At 1 week, few cells were observed at the midsubstance of the grafted tendon. A number of proliferating cells were observed at the surface area of the patellar tendon graft 2 weeks after graft transplantation, while no vessel formation was observed in the graft at the same time.VEGF was highly expressed 2-to-3 weeks postoperatively. Vessel formation in the patellar tendon graft increased with time from 3 week to 8 weeks after ACL reconstruction. The rates of proliferating cells and VEGF-expressing cells decreased with time from 3 week to 8 weeks. This study has suggested that VEGF is involved in the graft remodeling process particularly at the early phase after ACL reconstruction.

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Section: Discussionmentioning

confidence: 98%

Expression of vascular endothelial growth factor and angiogenesis in patellar tendon grafts in the early phase after anterior cruciate ligament reconstruction

Yoshikawa

Tohyama

Enomoto

et al. 2006

Knee Surg Sports Traumatol Arthr

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“…These results suggest that the sFlt-1 gene therapy is protective against focal brain ischemia, even after induction of brain ischemia. Several studies reported beneficial effects of VEGF on brain ischemia in vivo (Hayashi et al, 1998;Wang et al, 2005), and in vitro (Jin et al, 2000). However, there are several concerns over the VEGF therapy for acute brain ischemia because VEGF promotes vascular permeability.…”

Section: Discussionmentioning

confidence: 99%

Postischemic Gene Transfer of Soluble Flt-1 Protects against Brain Ischemia with Marked Attenuation of Blood—Brain Barrier Permeability

Kumai

Ooboshi

Ibayashi

et al. 2006

J Cereb Blood Flow Metab

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Brain edema is a major and often mortal complication of brain ischemia. Vascular endothelial growth factor (VEGF) is also known as a potent vascular permeability factor and may play detrimental roles at the acute stage of brain infarction. Our goal in this study was to explore protective effects of gene transfer of soluble flt-1 (sFlt-1), a natural inhibitor of VEGF, on focal brain ischemia. Adenoviral vector encoding sFlt-1 or b-galactosidase as control was injected into the lateral ventricle 90 mins after photochemical distal middle cerebral artery occlusion in male spontaneously hypertensive rats. The transduced sFlt-1 was released to the cerebrospinal fluid from the ventricular wall and significantly increased 6 h, 1 and 7 days after sFlt-1 transfection. One day after brain ischemia, sFlt-1 gene transfer significantly reduced infarct volume (by 35%), brain edema (by 35%), and blood-brain barrier permeability (Evans blue extravasation; by 69%) with diminished phosphorylation of focal adhesion kinase (FAKtyr397 and FAKtyr861) in the ischemic vessels. Seven days after ischemia, sFlt-1 gene transfer also significantly attenuated infarct volume (by 29%) and monocyte/macrophage infiltration (by 27%), although there were no reductions in angiogenesis by sFlt-1 overexpression. These results suggest that sFlt-1 gene therapy targeting brain edema in acute stage of brain ischemia may be useful for brain infarction.

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“…VEGF is expressed in astrocytes as well as other cell types. 106,107 VEGF induces angiogenesis, 108 has direct neuroprotective effects on neurons in culture, 109 and is important for inhibiting delayed neuronal death several days after stroke 28 (FIG. 2E).…”

Section: Figmentioning

confidence: 99%

Targeting Astrocytes for Stroke Therapy

2010

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Summary: Stroke remains a major health problem and is a leading cause of death and disability. Past research and neurotherapeutic clinical trials have targeted the molecular mechanisms of neuronal cell death during stroke, but this approach has uniformly failed to reduce stroke-induced damage or to improve functional recovery. Beyond the intrinsic molecular mechanisms inducing neuronal death during ischemia, survival and function of astrocytes is absolutely required for neuronal survival and for functional recovery after stroke. Many functions of astrocytes likely improve neuronal viability during stroke. For example, uptake of glutamate and release of neurotrophins enhances neuronal viability during ischemia. Under certain conditions, however, astrocyte function may compromise neuronal viability. For example, astrocytes may produce inflammatory cytokines or toxic mediators, or may release glutamate. The only clinical neurotherapeutic trial for stroke that specifically targeted astrocyte function focused on reducing release of S-100␤ from astrocytes, which becomes a neurotoxin when present at high levels. Recent work also suggests that astrocytes, beyond their influence on cell survival, also contribute to angiogenesis, neuronal plasticity, and functional recovery in the several days to weeks after stroke. If these delayed functions of astrocytes could be targeted for enhancing stroke recovery, it could contribute importantly to improving stroke recovery. This review focuses on both the positive and the negative influences of astrocytes during stroke, especially as they may be targeted for translation to human trials.

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Vascular endothelial growth factor: Direct neuroprotective effect in in vitro ischemia

Cited by 631 publications

References 51 publications

Expression of vascular endothelial growth factor and angiogenesis in patellar tendon grafts in the early phase after anterior cruciate ligament reconstruction

Expression of vascular endothelial growth factor and angiogenesis in patellar tendon grafts in the early phase after anterior cruciate ligament reconstruction

Postischemic Gene Transfer of Soluble Flt-1 Protects against Brain Ischemia with Marked Attenuation of Blood—Brain Barrier Permeability

Targeting Astrocytes for Stroke Therapy

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