Chen Yujie, Luo Chunxia, Zhao Mingyue, Li Qiang, Hu Rong, Zhang John H, Liu Zhi, Feng Hua
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
Department of Neurology, Southwest Hospital, Third Military Medical University, Chongqing, China.
Neurosci Lett. 2015 Feb 19;588:131-6. doi: 10.1016/j.neulet.2015.01.005. Epub 2015 Jan 6.
The aim of this study was to investigate whether the phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibitor dipotassium bisperoxo(pyridine-2-carboxyl) oxovanadate (BPV(pic)) attenuates early brain injury by modulating α-amino-3-hydroxy-5-methyl-4-isoxa-zolep-propionate (AMPA) receptor subunits after subarachnoid hemorrhage (SAH). A standard intravascular perforation model was used to produce the experimental SAH in Sprague-Dawley rats. BPV(pic) treatment (0.2mg/kg) was evaluated for effects on neurological score, brain water content, Evans blue extravasation, hippocampal neuronal death and AMPA receptor subunits alterations after SAH. We found that BPV(pic) is effective in attenuating BBB disruption, lowering edema, reducing hippocampal neural death and improving neurological outcomes. In addition, the AMPA receptor subunit GluR1 protein expression at cytomembrane was downregulated, whereas the expression of GluR2 and GluR3 was upregulated after BPV(pic) treatment. Our results suggest that PTEN inhibited by BPV(pic) plays a neuroprotective role in SAH pathophysiology, possibly by alterations in glutamate AMPA receptor subunits.
本研究旨在探讨10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）抑制剂双过氧（吡啶-2-羧基）氧钒二钾（BPV(pic)）在蛛网膜下腔出血（SAH）后是否通过调节α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体亚基来减轻早期脑损伤。采用标准的血管内穿刺模型在Sprague-Dawley大鼠中诱导实验性SAH。评估BPV(pic)治疗（0.2mg/kg）对SAH后神经功能评分、脑含水量、伊文思蓝外渗、海马神经元死亡和AMPA受体亚基改变的影响。我们发现BPV(pic)可有效减轻血脑屏障破坏、降低水肿、减少海马神经死亡并改善神经功能结局。此外，BPV(pic)治疗后，细胞膜上AMPA受体亚基GluR1蛋白表达下调，而GluR2和GluR3表达上调。我们的结果表明，BPV(pic)抑制的PTEN在SAH病理生理学中发挥神经保护作用，可能是通过谷氨酸AMPA受体亚基的改变实现的。
