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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.

Ding J, Guo J, Yuan Q, Yuan F, Chen H, Tian H - PLoS ONE (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Shanghai 6 th People's Hospital, Shanghai Jiaotong University, Shanghai, China.

ABSTRACT

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.

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Anatomical location of the histological sections: penumbra cortex.
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pone-0080429-g002: Anatomical location of the histological sections: penumbra cortex.

Mentions: For brain tissue preparation, rats were sacrificed under anesthesia at different time points. Before sacrifice, the chest was opened and perfused with 0.9% saline through the left ventricle until colorless perfusion fluid was obtained from the right atrium. Whole brains were removed for dissection. An 8×8-mm area of cortex containing the injury core was removed. At 2, 6, 24, 48, and 72 h after TBI, brains from sham controls, the bpV (pic)-treated group, and the non-bpV (pic)-treated group were collected for experiments. Tissues used for western blotting and real-time quantitative PCR (Q-PCR) were stored in liquid nitrogen and then at −80°C. For the TUNEL test, rats were perfused with 4% paraformaldehyde in 0.1 M phosphate buffer after saline perfusion, embedded in paraffin, and stored at −80°C. For immunostaining, tissues were perfused with 4% paraformaldehyde following 0.9% saline, and then immersed in 30% saccharobiose. Tissues were stored at −80°C after being embedded in optimal cutting temperature compound (OCT). The anatomical location of the histological sections used in the analyses is the penumbra cortex (Figure 2).


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.

Ding J, Guo J, Yuan Q, Yuan F, Chen H, Tian H - PLoS ONE (2013)

Anatomical location of the histological sections: penumbra cortex.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842922&req=5

pone-0080429-g002: Anatomical location of the histological sections: penumbra cortex.
Mentions: For brain tissue preparation, rats were sacrificed under anesthesia at different time points. Before sacrifice, the chest was opened and perfused with 0.9% saline through the left ventricle until colorless perfusion fluid was obtained from the right atrium. Whole brains were removed for dissection. An 8×8-mm area of cortex containing the injury core was removed. At 2, 6, 24, 48, and 72 h after TBI, brains from sham controls, the bpV (pic)-treated group, and the non-bpV (pic)-treated group were collected for experiments. Tissues used for western blotting and real-time quantitative PCR (Q-PCR) were stored in liquid nitrogen and then at −80°C. For the TUNEL test, rats were perfused with 4% paraformaldehyde in 0.1 M phosphate buffer after saline perfusion, embedded in paraffin, and stored at −80°C. For immunostaining, tissues were perfused with 4% paraformaldehyde following 0.9% saline, and then immersed in 30% saccharobiose. Tissues were stored at −80°C after being embedded in optimal cutting temperature compound (OCT). The anatomical location of the histological sections used in the analyses is the penumbra cortex (Figure 2).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Shanghai 6 th People's Hospital, Shanghai Jiaotong University, Shanghai, China.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus