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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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The process of FPI in rats.A: the FPI machine. B: injury site (arrow). C and D: brain tissue shows the injury core (arrows). E and F: MRI shows the injury core (arrows).
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pone-0080429-g001: The process of FPI in rats.A: the FPI machine. B: injury site (arrow). C and D: brain tissue shows the injury core (arrows). E and F: MRI shows the injury core (arrows).

Mentions: We used the unilateral rat FPI model in this study [15]. In brief, male Sprague-Dawley rats (250–300 g) were anesthetized with 4% chloral hydrate by intraperitoneal injection. The temperature was maintained at 37°C by a thermal heating pad. A craniotomy (approximately 4 mm in diameter) was performed at the right lateral skull, such that the medial edge of the craniotomy was approximately 2 mm from the midline suture, midway between the bregma and lambda. A polyethylene tube with an inner diameter of approximately 4 mm was fixed to the opening with cyanoacrylate adhesive and dental acrylic, filled with 0.9% isotonic saline, and attached to the FPI device. Rats were subjected to moderate extradural FPI with 2.1-atm injury. The duration of the waveform response due to fluid percussion was recorded as 12 to 15 ms. Then the scalp was sutured (Figure 1). Sham animals received the same surgical procedures except FPI. All the rats were returned to the temperature-controlled room via air conditioning and thermal heating pad. All of the surgical, injury, and animal care protocols described above were approved by the Scientific and Ethics Committee of Shanghai Jiaotong University.


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)

The process of FPI in rats.A: the FPI machine. B: injury site (arrow). C and D: brain tissue shows the injury core (arrows). E and F: MRI shows the injury core (arrows).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0080429-g001: The process of FPI in rats.A: the FPI machine. B: injury site (arrow). C and D: brain tissue shows the injury core (arrows). E and F: MRI shows the injury core (arrows).
Mentions: We used the unilateral rat FPI model in this study [15]. In brief, male Sprague-Dawley rats (250–300 g) were anesthetized with 4% chloral hydrate by intraperitoneal injection. The temperature was maintained at 37°C by a thermal heating pad. A craniotomy (approximately 4 mm in diameter) was performed at the right lateral skull, such that the medial edge of the craniotomy was approximately 2 mm from the midline suture, midway between the bregma and lambda. A polyethylene tube with an inner diameter of approximately 4 mm was fixed to the opening with cyanoacrylate adhesive and dental acrylic, filled with 0.9% isotonic saline, and attached to the FPI device. Rats were subjected to moderate extradural FPI with 2.1-atm injury. The duration of the waveform response due to fluid percussion was recorded as 12 to 15 ms. Then the scalp was sutured (Figure 1). Sham animals received the same surgical procedures except FPI. All the rats were returned to the temperature-controlled room via air conditioning and thermal heating pad. All of the surgical, injury, and animal care protocols described above were approved by the Scientific and Ethics Committee of Shanghai Jiaotong University.

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