title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These data suggest that treatment with the PTEN inhibitor bpV (pic) has a neuroprotective effect in TBI rats.
authors: Department of Neurosurgery, Shanghai 6 th People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors: Jun
authors: J
authors: Ding
authors: Jianyi
authors: J
authors: Guo
authors: Qiang
authors: Q
authors: Yuan
authors: Fang
authors: F
authors: Yuan
authors: Hao
authors: H
authors: Chen
authors: Hengli
authors: H
authors: Tian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000534:rehabilitation; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D033481:Chromosomes, Mammalian; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D009942:Organometallic Compounds / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D020127:Recovery of Function; D000070876:Tensins
chemical_list: D008840:Microfilament Proteins; D009942:Organometallic Compounds; D000070876:Tensins; C000603372:Tns1 protein, rat; C119540:oxodiperoxo(pyridine-2-carboxylate)vanadate(V); D051057:Proto-Oncogene Proteins c-akt; D010749:Phosphoprotein Phosphatases; D051059:PTEN Phosphohydrolase