Inhibition of phosphatase and tensin homolog deleted on chromosome 10 decreases rat cortical neuron injury and blood-brain barrier permeability, and improves neurological functional recovery in traumatic brain injury model.
Inhibition of phosphatase and tensin homolog deleted on chromosome 10 decreases rat cortical neuron injury and blood-brain barrier permeability, and improves neurological functional recovery in traumatic brain injury model.
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10 号染色体上删除的磷酸酶和张力蛋白同源物的抑制可减少大鼠皮质神经元损伤和血脑屏障通透性，并改善创伤性脑损伤模型中的神经功能恢复
DOI：
10.1371/journal.pone.0080429
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tian H
中科院分区：
文献类型：
--
作者：
Ding J;Guo J;Yuan Q;Yuan F;Chen H;Tian H
最近的证据支持bpV （pic）在缺血性卒中模型中的神经保护作用，bpV是一种磷酸酶和10号染色体上缺失的紧张素同源物（PTEN）的抑制剂。然而，PTEN抑制剂是否能改善创伤性脑损伤（TBI）后的长期功能恢复以及PTEN是否影响血脑屏障（BBB）的通透性还有待进一步研究。本研究就是为了解决这些问题。成年Sprague-Dawley大鼠在FPI前24小时开始使用成熟的PTEN抑制剂bpV （pic）或生理盐水治疗后进行液体撞击损伤（FPI）。采用Western blotting、实时定量PCR或免疫染色检测PTEN、p-Akt或MMP-9的表达。采用TUNEL法检测神经元凋亡的存在。测量Evans蓝染料外渗以评估血脑屏障破坏程度。采用神经功能严重程度评分（NSS）评估功能恢复情况，生存分析采用Kaplan-Meier分析。TBI后PTEN表达上调。bpV （pic）处理后，p-Akt也上调。我们发现bpV （pic）显著降低血脑屏障的通透性，减少tunel阳性细胞的数量。我们进一步证明PTEN抑制可改善TBI后早期的神经功能恢复。这些数据表明，PTEN抑制剂bpV （pic）治疗对TBI大鼠具有神经保护作用。
Recent evidence has supported the neuroprotective effect of bpV (pic), an inhibitor of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), in models of ischemic stroke. However, whether PTEN inhibitors improve long-term functional recovery after traumatic brain injury (TBI) and whether PTEN affects blood brain barrier (BBB) permeability need further elucidation. The present study was performed to address these issues. Adult Sprague-Dawley rats were subjected to fluid percussion injury (FPI) after treatment with a well-established PTEN inhibitor bpV (pic) or saline starting 24 h before FPI. Western blotting, real-time quantitative PCR, or immunostaining was used to measure PTEN, p-Akt, or MMP-9 expression. We determined the presence of neuron apoptosis by TUNEL assay. Evans Blue dye extravasation was measured to evaluate the extent of BBB disruption. Functional recovery was assessed by the neurological severity score (NSS), and Kaplan-Meier analysis was used for survival analysis. PTEN expression was up-regulated after TBI. After bpV (pic) treatment, p-Akt was also up-regulated. We found that bpV (pic) significantly decreased BBB permeability and reduced the number of TUNEL-positive cells. We further demonstrated that PTEN inhibition improved neurological function recovery in the early stage after TBI. These data suggest that treatment with the PTEN inhibitor bpV (pic) has a neuroprotective effect in TBI rats.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
3.7
作者：
Dasari VR;Kaur K;Velpula KK;Gujrati M;Fassett D;Klopfenstein JD;Dinh DH;Rao JS
通讯作者：
Rao JS
正常成年大鼠脑中 PTEN 的差异表达及缺血大脑皮层中 PTEN 和 p-Akt 的上调
DOI：
10.1002/ar.20834
发表时间：
2009-04-01
影响因子：
2
作者：
Cai, Qi-Yan;Chen, Xing-Shu;Yao, Zhong-Xiang
通讯作者：
Yao, Zhong-Xiang
影响因子：
4.8
作者：
Kini, Vidisha;Chavez, Alejandra;Mehta, Dolly
通讯作者：
Mehta, Dolly
DOI：
10.1152/ajpheart.00915.2009
发表时间：
2010-04-01
影响因子：
4.8
作者：
Keyes, Kyle T.;Xu, Jing;Ye, Yumei
通讯作者：
Ye, Yumei