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PPARγ upregulation induced by vagus nerve stimulation exerts anti-inflammatory effect in cerebral ischemia/reperfusion rats.

Jiang Y, Li L, Liu B, Zhang Y, Chen Q, Li C - Med. Sci. Monit. (2015)

Bottom Line: The expression of PPARγ after VNS treatment was measured by real-time PCR and Western blotting, also supported by immunofluorescence staining.Additionally, the influence on the pro-inflammatory cytokines expression and neuro-immune cells activation was determined by ELISA and immunofluorescence staining.We found that VNS upregulated expression of PPARγ in ischemia penumbra, diminished the extent of ischemic infarct, alleviated neuronal injury, and suppressed pro-inflammatory cytokine expression and immune cell activation (P<0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland).

ABSTRACT

Background: It is well known that peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activated transcription factor, plays a protective role in anti-inflammatory responses in both acute and chronic central nerve system (CNS) insults. Emerging evidence in rats suggests that vagus nerve stimulation (VNS), while restraining inflammatory cytokine production in the peripheral nervous system, also exerts a significant CNS neuroprotective function against ischemic stroke injury. The aim of this study was to explore the role of PPARγ in VNS-mediated anti-inflammatory protection against ischemic stroke damage.

Material/methods: Adult male Sprague-Dawley rats (total n=160) preconditioned through transfection with either PPARγ small interfering RNA (siRNA) or lentiviral vector without siRNA and surgically subjected to middle cerebral artery occlusion and reperfusion subsequently received VNS treatment at 30 min post-occlusion. The expression of PPARγ after VNS treatment was measured by real-time PCR and Western blotting, also supported by immunofluorescence staining. Subsequently, the neurological deficits scores, the infarct volume, and the brain histopathology were all evaluated. Additionally, the influence on the pro-inflammatory cytokines expression and neuro-immune cells activation was determined by ELISA and immunofluorescence staining.

Results: We found that VNS upregulated expression of PPARγ in ischemia penumbra, diminished the extent of ischemic infarct, alleviated neuronal injury, and suppressed pro-inflammatory cytokine expression and immune cell activation (P<0.05). However, rats with PPARγ silencing failed to manifest significant neuroprotection and anti-inflammatory effect induced by VNS treatment (p>0.05).

Conclusions: PPARγ may participate in the process by which VNS modulates the neuro-inflammatory response following ischemia/reperfusion in rats.

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Related in: MedlinePlus

Neuroprotective effect induced by VNS was reduced after PPARr silencing during cerebral I/R insult. VNS improved the neurological deficits scores and reduced the cerebral infarct volume at 24 h post-reperfusion in rats. However, after PPRAr silencing, there were no significant differences in neurological recovery and infarct volume between I/R+LV-shPPARr and I/R+VNS+LV-shPPARr group. Data are mean ± SEM. *p<0.05 compared with I/R+ LV-control group. A: I/R+ LV-control group, B: I/R+VNS+LV-control group, C: I/R+LV-shPPARr group, D: I/R+VNS+ LV-shPPARr group.
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f2-medscimonit-21-268: Neuroprotective effect induced by VNS was reduced after PPARr silencing during cerebral I/R insult. VNS improved the neurological deficits scores and reduced the cerebral infarct volume at 24 h post-reperfusion in rats. However, after PPRAr silencing, there were no significant differences in neurological recovery and infarct volume between I/R+LV-shPPARr and I/R+VNS+LV-shPPARr group. Data are mean ± SEM. *p<0.05 compared with I/R+ LV-control group. A: I/R+ LV-control group, B: I/R+VNS+LV-control group, C: I/R+LV-shPPARr group, D: I/R+VNS+ LV-shPPARr group.

Mentions: Rats with PPARr silencing or without were pretreated as described in the Methods section above. Subsequent to transient MCAO and VNS treatment at 24 h, neurological-deficits scores and infarct sizes were evaluated. Results showed that VNS significantly improved neurological scores and decreased infarct volume compared to that in the I/R+LV-control group (p<0.05), while after PPARr silencing there were no significant differences in neurological scores and brain infarct size when comparing the I/R+VNS+ PPARrsiRNA group with compared I/R+VNS+ LV-shPPARr with I/R+LV-shPPARr group. As shown in Figure 2, these results suggest that PPARr was involved in the beneficial effects of VNS on transient cerebral I/R+LV-control group in rat.


PPARγ upregulation induced by vagus nerve stimulation exerts anti-inflammatory effect in cerebral ischemia/reperfusion rats.

Jiang Y, Li L, Liu B, Zhang Y, Chen Q, Li C - Med. Sci. Monit. (2015)

Neuroprotective effect induced by VNS was reduced after PPARr silencing during cerebral I/R insult. VNS improved the neurological deficits scores and reduced the cerebral infarct volume at 24 h post-reperfusion in rats. However, after PPRAr silencing, there were no significant differences in neurological recovery and infarct volume between I/R+LV-shPPARr and I/R+VNS+LV-shPPARr group. Data are mean ± SEM. *p<0.05 compared with I/R+ LV-control group. A: I/R+ LV-control group, B: I/R+VNS+LV-control group, C: I/R+LV-shPPARr group, D: I/R+VNS+ LV-shPPARr group.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4310716&req=5

f2-medscimonit-21-268: Neuroprotective effect induced by VNS was reduced after PPARr silencing during cerebral I/R insult. VNS improved the neurological deficits scores and reduced the cerebral infarct volume at 24 h post-reperfusion in rats. However, after PPRAr silencing, there were no significant differences in neurological recovery and infarct volume between I/R+LV-shPPARr and I/R+VNS+LV-shPPARr group. Data are mean ± SEM. *p<0.05 compared with I/R+ LV-control group. A: I/R+ LV-control group, B: I/R+VNS+LV-control group, C: I/R+LV-shPPARr group, D: I/R+VNS+ LV-shPPARr group.
Mentions: Rats with PPARr silencing or without were pretreated as described in the Methods section above. Subsequent to transient MCAO and VNS treatment at 24 h, neurological-deficits scores and infarct sizes were evaluated. Results showed that VNS significantly improved neurological scores and decreased infarct volume compared to that in the I/R+LV-control group (p<0.05), while after PPARr silencing there were no significant differences in neurological scores and brain infarct size when comparing the I/R+VNS+ PPARrsiRNA group with compared I/R+VNS+ LV-shPPARr with I/R+LV-shPPARr group. As shown in Figure 2, these results suggest that PPARr was involved in the beneficial effects of VNS on transient cerebral I/R+LV-control group in rat.

Bottom Line: The expression of PPARγ after VNS treatment was measured by real-time PCR and Western blotting, also supported by immunofluorescence staining.Additionally, the influence on the pro-inflammatory cytokines expression and neuro-immune cells activation was determined by ELISA and immunofluorescence staining.We found that VNS upregulated expression of PPARγ in ischemia penumbra, diminished the extent of ischemic infarct, alleviated neuronal injury, and suppressed pro-inflammatory cytokine expression and immune cell activation (P<0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland).

ABSTRACT

Background: It is well known that peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activated transcription factor, plays a protective role in anti-inflammatory responses in both acute and chronic central nerve system (CNS) insults. Emerging evidence in rats suggests that vagus nerve stimulation (VNS), while restraining inflammatory cytokine production in the peripheral nervous system, also exerts a significant CNS neuroprotective function against ischemic stroke injury. The aim of this study was to explore the role of PPARγ in VNS-mediated anti-inflammatory protection against ischemic stroke damage.

Material/methods: Adult male Sprague-Dawley rats (total n=160) preconditioned through transfection with either PPARγ small interfering RNA (siRNA) or lentiviral vector without siRNA and surgically subjected to middle cerebral artery occlusion and reperfusion subsequently received VNS treatment at 30 min post-occlusion. The expression of PPARγ after VNS treatment was measured by real-time PCR and Western blotting, also supported by immunofluorescence staining. Subsequently, the neurological deficits scores, the infarct volume, and the brain histopathology were all evaluated. Additionally, the influence on the pro-inflammatory cytokines expression and neuro-immune cells activation was determined by ELISA and immunofluorescence staining.

Results: We found that VNS upregulated expression of PPARγ in ischemia penumbra, diminished the extent of ischemic infarct, alleviated neuronal injury, and suppressed pro-inflammatory cytokine expression and immune cell activation (P<0.05). However, rats with PPARγ silencing failed to manifest significant neuroprotection and anti-inflammatory effect induced by VNS treatment (p>0.05).

Conclusions: PPARγ may participate in the process by which VNS modulates the neuro-inflammatory response following ischemia/reperfusion in rats.

Show MeSH
Related in: MedlinePlus