Treatment for acute/chronic ischemic neuronal injury using vanadate

原钒酸盐是蛋白酪氨酸磷酸酶的竞争性抑制剂。一些已报道的生物效应是其胰岛素模拟特性和激活磷酸肌肽3-激酶和细胞外信号调节激酶（ERK）。作者先前报道了其通过Akt和ERK激活沙鼠海马CA1神经元在短暂性前脑缺血后延迟神经元死亡的神经保护作用。本研究研究了脑缺血后腹腔注射原钒酸钠（50 mmol/l生理盐水中原钒酸钠2 l/kg）对大脑中动脉闭塞大鼠的神经保护作用。缺血后1天和28天分别评价神经元的缺血性损伤。在缺血后1天和28天，正钒酸盐对皮质的神经保护作用显著，而对尾状壳核（缺血核心）的神经保护作用不显著。原钒酸盐组再灌注后Akt、ERK活性维持；生理盐水组明显减少。血糖水平下降，但在正常范围内。仅在再灌注后0 h，局部脑血流量低于生理盐水组。这些数据表明，原钒酸盐对短暂性大脑中动脉闭塞大鼠具有神经保护作用，这种作用是通过激活Akt和ERK介导的。此外，低血糖水平和局部脑血流的逐渐恢复可能有助于神经保护。缺血后注射钒酸钠。SVZ组Budr/double cortin阳性细胞数量明显减少。由此可见，钒酸盐对缺血后的祖细胞有诱导作用。钒酸盐可能具有诱导神经元再生的潜力。需要进一步的调查和治疗试验。

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.