Expression of vascular endothelial growth factor mRNA following transient forebrain ischemia in rats

Lee, Mun‐Yong; Ju, Won‐Kyu; Cha, Jung-Ho; Son, Byung Chul; Chun, Myung-Hoon; Kang, Jonghoon; Park, Chun Kun

doi:10.1016/s0304-3940(99)00219-0

Cited by 74 publications

(41 citation statements)

References 14 publications

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“…The levels of VEGF mRNA in ear skin of K14-HIF-1␣⌬ODD transgenic mice is similar to the 13-to 25-fold elevation of VEGF expression produced by hypoxia in cultured cells (Ikeda et al 1995;Levy et al 1995Levy et al , 1996bStein et al 1998). HIF-1␣⌬ODD-mediated VEGF mRNA induction is within range, although higher, than the 2.5-to 8-fold increase in VEGF mRNA levels in hypoxic tissues (Banai et al 1994;Lee et al 1999;Miraliakbari et al 2000). These differences may be due to sensitivity of the real-time RT-PCR used here, compared with the Northern analysis used in prior work.…”

Section: Determination Of Total Vegf Mrna and Protein Expressionmentioning

confidence: 77%

Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1α

Elson¹,

Thurston²,

Huang³

et al. 2001

Genes Dev.

280

222

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Hypoxia-inducible factor-1␣ (HIF-1␣) transactivates genes required for energy metabolism and tissue perfusion and is necessary for embryonic development and tumor explant growth. HIF-1␣ is overexpressed during carcinogenesis, myocardial infarction, and wound healing; however, the biological consequences of HIF-1␣ overexpression are unknown. Here, transgenic mice expressing constitutively active HIF-1␣ in epidermis displayed a 66% increase in dermal capillaries, a 13-fold elevation of total vascular endothelial growth factor (VEGF) expression, and a six-to ninefold induction of each VEGF isoform. Despite marked induction of hypervascularity, HIF-1␣ did not induce edema, inflammation, or vascular leakage, phenotypes developing in transgenic mice overexpressing VEGF cDNA in skin. Remarkably, blood vessel leakage resistance induced by HIF-1␣ overexpression was not caused by up-regulation of angiopoietin-1 or angiopoietin-2. Hypervascularity induced by HIF-1␣ could improve therapy of tissue ischemia.

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Section: Determination Of Total Vegf Mrna and Protein Expressionmentioning

confidence: 77%

Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1α

Elson¹,

Thurston²,

Huang³

et al. 2001

Genes Dev.

280

222

View full text Add to dashboard Cite

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“…8 B). VEGF synthesis by astrocytes associated with de novo neurogenesis has already been observed during postnatal development of the cerebellum (Acker et al, 2001), in brains subjected to enriched environments and performance in the hippocampus (Cao et al, 2004) and after brain injury (Lee et al, 1999). Thus, specialized astrocytes of the neurogenic regions are an endogenous source of VEGF that might contribute to directed migration of neural progenitors.…”

Section: Astrocytes Of the Neurogenic Svz And The Rms Areas Express Vegfmentioning

confidence: 97%

IQGAP1 Regulates Adult Neural ProgenitorsIn Vivoand Vascular Endothelial Growth Factor-Triggered Neural Progenitor MigrationIn Vitro

Balenci¹,

Saoudi²,

Grünwald³

et al. 2007

J. Neurosci.

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In the germinative zone of the adult rodent brain, neural progenitors migrate into niches delimited by astrocyte processes and differentiate into neuronal precursors. In the present study, we report a modulating role for the scaffolding protein IQGAP1 in neural progenitor migration. We have identified IQGAP1 as a new marker of amplifying neural progenitor and neuronal precursor cells of the subventricular zone (SVZ) and the rostral migratory stream (RMS) in the adult mouse brain. To determine functions for IQGAP1 in neural progenitors, we compared the properties of neural progenitor cells from wild-type and Iqgap1-null mutant mice in vivo and in vitro. The in vivo studies reveal a delay in the transition of de novo neural progenitors into neuronal precursor cells in Iqgap1-null mice. In vitro, we demonstrated that IQGAP1 acts as a downstream effector in the vascular endothelial growth factor (VEGF)-dependent migratory response of neural progenitors that also impacts on their neuronal differentiation. The Rho-family GTPases cdc42/Rac1 and Lis1 are major partners of IQGAP1 in this migratory process. Finally, astrocytes of the neurogenic SVZ and RMS are shown to express VEGF. We propose that VEGF synthesized by astrocytes could be involved in the guidance of neural progenitors to neurogenic niches and that IQGAP1 is an effector of the VEGF-dependent migratory signal.

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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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Expression of vascular endothelial growth factor mRNA following transient forebrain ischemia in rats

Cited by 74 publications

References 14 publications

Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1α

Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1α

IQGAP1 Regulates Adult Neural ProgenitorsIn Vivoand Vascular Endothelial Growth Factor-Triggered Neural Progenitor MigrationIn Vitro

Targeting Astrocytes for Stroke Therapy

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