Department of Neurosurgery, Shanghai 6 th People's Hospital, Shanghai Jiaotong University, Shanghai, China.
PLoS One. 2013 Nov 28;8(11):e80429. doi: 10.1371/journal.pone.0080429. eCollection 2013.
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.
最近的证据支持磷酸酶和张力蛋白同源物缺失的第 10 号染色体（PTEN）抑制剂 bpV（pic）在缺血性中风模型中的神经保护作用。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）通透性，仍需要进一步阐明。本研究旨在解决这些问题。
成年 Sprague-Dawley 大鼠在 FPI 前 24 小时开始用已建立的 PTEN 抑制剂 bpV（pic）或生理盐水处理，然后进行液压冲击伤（FPI）。Western blot、实时定量 PCR 或免疫染色用于测量 PTEN、p-Akt 或 MMP-9 的表达。我们通过 TUNEL 检测来确定神经元凋亡的存在。通过 Evans Blue 染料渗出来评估 BBB 破坏的程度。通过神经功能缺损评分（NSS）评估功能恢复，采用 Kaplan-Meier 分析进行生存分析。
TBI 后 PTEN 表达上调。bpV（pic）治疗后，p-Akt 也上调。我们发现 bpV（pic）可显著降低 BBB 通透性并减少 TUNEL 阳性细胞数。我们进一步表明，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。
