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
| Autor: | Jian-Yi Guo, Jun Ding, Qiang Yuan, Fang Yuan, Heng-Li Tian, Hao Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Traumatic brain injury Phosphatase lcsh:Medicine Apoptosis Brain damage Blood–brain barrier Neuroprotection Permeability Tensins medicine Organometallic Compounds Phosphoprotein Phosphatases Tensin PTEN Animals lcsh:Science Cerebral Cortex Neurons Multidisciplinary biology lcsh:R Microfilament Proteins PTEN Phosphohydrolase Recovery of Function biochemical phenomena metabolism and nutrition medicine.disease Molecular biology Chromosomes Mammalian Rats Disease Models Animal medicine.anatomical_structure Gene Expression Regulation Cerebral cortex Blood-Brain Barrier Brain Injuries Cancer research biology.protein lcsh:Q medicine.symptom Proto-Oncogene Proteins c-akt Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 11, p e80429 (2013) |
| ISSN: | 1932-6203 |
| Popis: | Background and Purpose 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. Conclusion These data suggest that treatment with the PTEN inhibitor bpV (pic) has a neuroprotective effect in TBI rats. |
| Databáze: | OpenAIRE |
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