Effects of Anti-VEGF Antibody on Blood-Brain Barrier Disruption in Focal Cerebral Ischemia

Oz, Chi; Hunter, Christine; Liu, X; Weiss, HR

doi:10.1097/00008506-200610000-00038

Cited by 11 publications

(13 citation statements)

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“…100 g of anti-VEGF antibody (immunogen, human recombinant VEGF-165; Lab Vision Corp., Fremont, Calif., USA) was topically applied on IC-2 for a period of 90 min before the BBB was disrupted with mannitol. This dose of anti-VEGF antibody was effective in reducing BBB disruption caused by focal cerebral ischemia [11] .…”

Section: Methodsmentioning

confidence: 93%

“…It has been reported that VEGF is in part responsible for the plasma extravasation associated with cerebral edema in conditions such as cerebral ischemia, hypoxia, brain injury and brain tumor [7][8][9][10][11] . Since VEGF is involved in BBB disruption in various conditions, we speculated that it would also play a role in the disruption of the BBB by hyperosmolar solution.…”

Section: Introductionmentioning

confidence: 99%

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Effects of VEGF on the Blood-Brain Barrier Disruption Caused by Hyperosmolarity

Z.¹,

Hunter

Liu

et al. 2008

Pharmacology

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This study was performed to test whether disruption of the blood-brain barrier (BBB) caused by hyperosmolarity could be related to vascular endothelial growth factor (VEGF), using anti-VEGF antibody and ciclopirox olamine (CPX), an inducer of VEGF. CPX 50 mg/kg or normal saline was given intraperitoneally to male Wistar rats 18 h before BBB disruption. Two craniotomies were made on the ipsilateral cortex (IC-1 and IC-2) where the BBB would be disrupted, and a third hole was made on the contralateral cortex (CC) to expose the cortices. We applied normal saline (to IC-1 and the CC) or anti-VEGF antibody (to IC-2) for 90 min before BBB disruption with intracarotid injection of 25% mannitol. The degree of BBB disruption was determined by measuring the transfer coefficient (K_i) of ¹⁴C-α-aminoisobutyric acid and the volume of ³H-dextran distribution. The protein levels of VEGF were determined with Western blot analysis. In the control animals, hyperosmolar mannitol significantly increased (415%) the K_i in IC-1. The K_i was attenuated with anti-VEGF antibody application (–28%, p < 0.05). Even though the protein levels of VEGF were strongly increased with CPX pretreatment, this upregulation did not alter the hyperosmolar BBB disruption in the saline- or in the antibody-treated cortex. The data on the volume of dextran distribution followed the same pattern as that of the K_i but without a statistically significant difference between IC-1 and IC-2 in either group. Our data demonstrated that hyperosmolar BBB disruption could be attenuated with anti-VEGF antibody. However, upregulation of VEGF with CPX did not alter the degree of hyperosmolar BBB disruption with or without anti-VEGF antibody treatment. This study suggests that the contribution of VEGF in hyperosmolar BBB disruption is limited.

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Section: Methodsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Effects of VEGF on the Blood-Brain Barrier Disruption Caused by Hyperosmolarity

Z.¹,

Hunter

Liu

et al. 2008

Pharmacology

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“…This dual role has also been observed for some target genes of HIF-1. For instance, whereas VEGF has been found to have neuroprotective properties under different conditions (Sun and Guo, 2005;Wang et al, 2006), other experimental approaches indicate that VEGF increases vascular permeability and inflammation, thus favoring cerebral edema (Lafuente et al, 2002;Althaus et al, 2006;Chi et al, 2007). In the same sense, a recent report has shown that administration of 2-methoxyestradiol and tricyclodecan-9-ylxanthogenate, two negative regulators of HIF-1, have neuroprotective effects in a model of focal ischemia induced by middle cerebral artery occlusion (MCAO; Chen et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotection by hypoxic preconditioning involves upregulation of hypoxia‐inducible factor‐1 in a prenatal model of acute hypoxia

Giusti

Plazas

2011

J of Neuroscience Research

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The molecular pathways underlying the neuroprotective effects of preconditioning are promising, potentially drugable targets to promote cell survival. However, these pathways are complex and are not yet fully understood. In this study we have established a paradigm of hypoxic preconditioning based on a chick embryo model of normobaric acute hypoxia previously developed by our group. With this model, we analyzed the role of hypoxia-inducible factor-1α (HIF-1α) stabilization during preconditioning in HIF-1 signaling after the hypoxic injury and in the development of a neuroprotective effect against the insult. To this end, we used a pharmacological approach, based on the in vivo administration of positive (Fe(2+), ascorbate) and negative (CoCl(2)) modulators of the activity of HIF-prolyl hydroxylases (PHDs), the main regulators of HIF-1. We have found that preconditioning has a reinforcing effect on HIF-1 accumulation during the subsequent hypoxic injury. In addition, we have also demonstrated that HIF-1 induction during hypoxic preconditioning is necessary to obtain an enhancement in HIF-1 accumulation and to develop a tolerance against a subsequent hypoxic injury. We provide in vivo evidence that administration of Fe(2+) and ascorbate modulates HIF accumulation, suggesting that PHDs might be targets for neuroprotection in the CNS.

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“…Так, ангіогенез у перифокальній зоні характеризується ранньою надмірною (у 1-й тиждень), подальшою декострукцією та неповноцінним дозріванням збере-жених судин (до кінця 1-го місяця), їх відтермінова-ною деконструкцією з супутнім аутоімунним, згодом -ішемічним ураженням перифокальної зони (2-3-й місяць) [59,61,62]. Стимуляція ангіогенезу у най-гострішому та ранньому періоді після травми може мати не лише позитивний метаботропний ефект, а й спричиняти репефузійне ураження [63,64] або формування значної кількості новоутворених судин з неповноцінною бар'єрною функцією, тобто, потен-ціювати подальший аутоімунний процес. З високою вірогідністю з матеріалів, що використовували у досліджені, концентрація основного ангіогенного фактору VEGF максимальна у тканині фетальної нирки, менша -зрілої нюхової цибулини, мінімальна -фетального мозочка [48,[65][66][67][68].…”

Section: непрямі впливи трансплантатів на збуд-ливість нейронів сусідunclassified

The influence of neurotransplantation with different allogenic tissues on the course of the spasticity and chronic pain syndrome after experimental spinal cord injury

Medvediev

2017

Ukr Neurosurg J

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Effects of Anti-VEGF Antibody on Blood-Brain Barrier Disruption in Focal Cerebral Ischemia

Cited by 11 publications

References 0 publications

Effects of VEGF on the Blood-Brain Barrier Disruption Caused by Hyperosmolarity

Effects of VEGF on the Blood-Brain Barrier Disruption Caused by Hyperosmolarity

Neuroprotection by hypoxic preconditioning involves upregulation of hypoxia‐inducible factor‐1 in a prenatal model of acute hypoxia

The influence of neurotransplantation with different allogenic tissues on the course of the spasticity and chronic pain syndrome after experimental spinal cord injury

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