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Treatment for acute/chronic ischemic neuronal injury using vanadate

钒酸盐治疗急/慢性缺血性神经元损伤

基本信息

批准号：
15591534
负责人：
MORIOKA Motohiro
金额：
$ 1.98万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591534/
关键词：
ischemia MCA occlusion vanadate apoptosis Akt ERK

项目摘要

Orthovanadate is a competitive inhibitor of protein tyrosine phosphatases. Some of its reported biologic effects are its insulin mimetic property and its activation of phosphoinositide 3-kinase and extracellular-signal regulated kinase(ERK). The authors previously reported its neuroprotective effect on delayed neuronal death of gerbil hippocampal CA1 neurons via Akt and ERK activation after transient forebrain ischemia. In the present study, the neuroprotective effect of postischemic intraperitoneal administration of sodium orthovanadate(2 l/kg of 50-mmol/l sodium orthovanadate in saline) was investigated in rats with transient middle cerebral artery occlusion. Ischemic neuronal injury was evaluated 1 day and 28 days after ischemia. The neuroprotective effect of orthovanadate was significant in the cortex but not the caudate putamen(ischemic core) at both 1 and 28 days after ischemia. In orthovanadate group, the activities of Akt and ERK were maintained after reperfusion ; they were decreased in saline group. Blood glucose level decreased but within normal range.Regional cerebral blood flow was lower than that of saline group only at 0 hours after reperfusion. These data suggest that orthovanadate has neuroprotective effects in rats with transient middle cerebral artery occlusion and that these effects are mediated by Akt and ERK activation. Furthermore, low blood glucose levels and gradual recovery of regional cerebral blood flow may contribute to neuroprotection.Next, we injected vanadte after ischemia. The number of Budr/double cortin positive cells decreased remarkably in SVZ. Thus we concluded that vanadate induced progenitor cells after ischemia.Vanadate may have a potential that induced neuronal regeneration. Further investigation and trial for treatment were needed.

正钒酸盐是蛋白酪氨酸磷酸酶的竞争性抑制剂。一些报道的生物学效应是其胰岛素模拟特性和其磷酸肌醇3-激酶和细胞外信号调节激酶（ERK）的激活。作者先前报道了其通过Akt和ERK激活对短暂前脑缺血后沙土鼠海马CA 1区神经元迟发性神经元死亡的神经保护作用。在本研究中，缺血后腹腔注射原钒酸钠（2 L/kg的50 mmol/L原钒酸钠的生理盐水）的神经保护作用进行了研究，在大鼠短暂的大脑中动脉闭塞。缺血后1天和28天评价缺血性神经元损伤。在缺血后1天和28天，原钒酸盐的神经保护作用在皮质中是显著的，但在尾壳核（缺血核心）中不是。原钒酸钠组再灌注后Akt和ERK活性维持不变，生理盐水组Akt和ERK活性降低。血糖水平下降，但在正常范围内，局部脑血流量仅在再灌注0小时低于生理盐水组。这些数据表明，原钒酸盐具有短暂性大脑中动脉闭塞大鼠的神经保护作用，这些作用是由Akt和ERK激活介导的。此外，低血糖水平和局部脑血流量的逐渐恢复可能有助于神经保护。SVZ中Budr/双皮质素阳性细胞数明显减少。因此，我们认为钒酸盐可以诱导缺血后的神经祖细胞，钒酸盐可能具有诱导神经元再生的潜力。需要进一步的研究和治疗试验。