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首页> 外文期刊>Translational Stroke Research >Delayed VEGF Treatment Enhances Angiogenesis and Recovery After Neonatal Focal Rodent Stroke
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Delayed VEGF Treatment Enhances Angiogenesis and Recovery After Neonatal Focal Rodent Stroke

机译：延迟的VEGF治疗可增强新生儿局灶性鼠中风后的血管生成和恢复。

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摘要

Neonatal stroke occurs in one in 4,000 live births and leads to significant morbidity and mortality. Approximately two thirds of the survivors have long-term sequelae including seizures and neurological deficits. However, the pathophysiological mechanisms of recovery after neonatal stroke are not clearly understood, and preventive measures and treatments are nonexistent in the clinical setting. In this study, we investigated the effect of vascular endothelial growth factor (VEGF) treatment on histological recovery and angiogenic response to the developing brain after an ischemic insult. Ten-day-old Sprague–Dawley rats underwent right middle cerebral arterial occlusion (MCAO) for 1.5 h. Diffusion-weighted MRI during occlusion confirmed focal ischemia that was then followed by reperfusion. On group of animals received 5-bromo-2-deoxyuridine and sacrificed at postnatal day (P)18 or P25. A second group of animals was treated with VEGF (1.5 μg/kg, icv) or phosphate-buffered saline (PBS) at P18 and perfusion fixed at P25. Based on Nissl and iron staining, a single VEGF injection reduced the injury score, compared to the animals that underwent MCAO and PBS injection. Furthermore, neurodegeneration represented by neuronal nuclei staining was markedly diminished. In addition, animals treated with VEGF revealed a positive trend in endothelial proliferation and a significant increase in total vessel volume in the peri-infarct region of the caudate. The number of Iba1-positive microglial cells was significantly reduced after a single VEGF injection, and myelin basic protein expression was enhanced in the caudate after ischemia without an effect of VEGF treatment. In conclusion, delayed treatment with VEGF ameliorates injury, promotes endothelial cell proliferation, and increases total vascular volume following neonatal stroke. These results suggest that VEGF has a neuroprotective effect, in part by enhancing endogenous angiogenesis. These data contribute to a better understanding of neonatal stroke.
机译：新生儿中风发生在4,000例活产中，其中有1例导致明显的发病率和死亡率。大约三分之二的幸存者患有包括癫痫发作和神经功能缺损在内的长期后遗症。但是，尚不清楚新生儿中风后恢复的病理生理机制，并且在临床环境中不存在预防措施和治疗方法。在这项研究中，我们调查了缺血性损伤后血管内皮生长因子（VEGF）处理对发育中的大脑的组织学恢复和血管生成反应的影响。十天大的Sprague–Dawley大鼠经过右脑中动脉闭塞（MCAO）1.5小时。闭塞过程中的弥散加权MRI证实为局灶性局部缺血，然后再灌注。在一组动物中，接受5-溴-2-脱氧尿苷并在出生后第（P）18或P25处死。第二组动物在P18处接受VEGF（1.5μg/ kg，icv）或磷酸盐缓冲盐水（PBS）处理，并在P25处固定灌注。基于Nissl和铁染色，与进行MCAO和PBS注射的动物相比，单次VEGF注射降低了损伤评分。此外，以神经元核染色为代表的神经变性明显减少。另外，用VEGF治疗的动物在尾状核的梗塞周围区域中显示出内皮增殖的积极趋势和总血管体积的显着增加。单次VEGF注射后，Iba1阳性小胶质细胞的数量显着减少，缺血后尾状组织中髓磷脂碱性蛋白表达增加，而没有VEGF治疗的作用。总之，延迟治疗VEGF可减轻损伤，促进内皮细胞增殖并增加新生儿卒中后的总血管体积。这些结果表明VEGF具有神经保护作用，部分是通过增强内源性血管生成来实现的。这些数据有助于更好地了解新生儿中风。

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  • 来源
    《Translational Stroke Research》 |2013年第2期|189-200|共12页
  • 作者

    M. Dzietko; N. Derugin; M. F. Wendland; Z. S. Vexler; D. M. Ferriero;

  • 作者单位

    Department of Pediatrics University of California San Francisco">(1);

    Klinik für Kinderheilkunde I Universitätsklinikum Essen">(4);

    Department of Neurology University of California San Francisco">(2);

    Department of Radiology University of California">(3);

    Department of Neurology University of California San Francisco">(2);

    Department of Pediatrics University of California San Francisco">(1);

    Department of Neurology University of California San Francisco">(2);

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  • 正文语种 eng
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  • 关键词

    VEGF; Neuroprotection; Angiogenesis; Neonatal stroke;

    机译：VEGF;神经保护;血管生成;新生儿中风;

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