Delayed VEGF treatment enhances angiogenesis and recovery after neonatal focal rodent stroke.
Delayed VEGF treatment enhances angiogenesis and recovery after neonatal focal rodent stroke.
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DOI：
10.1007/s12975-012-0221-6
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发表时间：
2013-04
影响因子：
6.9
通讯作者：
Ferriero, D. M.
中科院分区：
文献类型：
--
作者：
Dzietko, M.;Derugin, N.;Wendland, M. F.;Vexler, Z. S.;Ferriero, D. M.
新生儿中风的发生率为每4，000名活产婴儿中就有一名，并导致严重的发病率和死亡率。大约三分之二的幸存者有长期后遗症，包括癫痫发作和神经功能缺损。然而，新生儿卒中后恢复的病理生理机制尚不清楚，临床上也不存在预防措施和治疗方法。在这项研究中，我们研究了血管内皮生长因子（VEGF）治疗对缺血损伤后发育中大脑组织学恢复和血管生成反应的影响。10日龄Sprague-Dawley大鼠右侧大脑中动脉闭塞（MCAO）1.5 h。闭塞期间的弥散加权MRI证实局灶性缺血，然后再灌注。一组动物接受5-溴-2-脱氧尿苷，并在出生后第18天（P）或第25天处死。第二组动物在P18时用VEGF（1.5 µg/kg，icv）或磷酸盐缓冲盐水（PBS）处理，并在P25时灌注固定。基于尼氏染色和铁染色，与接受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显著减少。此外，用VEGF治疗的动物显示出内皮细胞增殖的积极趋势和尾状核梗塞周围区域总血管体积的显著增加。Iba 1阳性小胶质细胞的数量显着减少后，一个单一的VEGF注射，和髓鞘碱性蛋白表达增强缺血后的尾状核没有VEGF治疗的影响。总之，延迟VEGF治疗可改善损伤，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，部分通过增强内源性血管生成。这些数据有助于更好地了解新生儿卒中。
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.
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DOI：
10.1523/jneurosci.2102-11.2011
发表时间：
2011-09-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Faustino JV;Wang X;Johnson CE;Klibanov A;Derugin N;Wendland MF;Vexler ZS
通讯作者：
Vexler ZS
影响因子：
5.3
作者：
Ohab, John J.;Fleming, Sheila;Carmichael, S. Thomas
通讯作者：
Carmichael, S. Thomas
影响因子：
2.9
作者：
Hayashi, T;Iwai, M;Abe, K
通讯作者：
Abe, K
影响因子：
2.5
作者：
Hayakawa K;Seo JH;Pham LD;Miyamoto N;Som AT;Guo S;Kim KW;Lo EH;Arai K
通讯作者：
Arai K
影响因子：
2.6
作者：
Acker, T;Beck, H;Plate, KH
通讯作者：
Plate, KH