Limits...
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.

Show MeSH

Related in: MedlinePlus

The level of pro-inflammatory cytokines expression at 24 h post-reperfusion. (A) TNF-α and IL-1β in cerebral ischemic penumbra determined by ELISA. Data are presented as mean ±SEM. (*p<0.05 vs. I/R+ vehicle control group). (B) The number of activated astrocytes and microglia increased after transfection with PPARγ siRNA. Scale bar=75 μm. 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.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4310716&req=5

f4-medscimonit-21-268: The level of pro-inflammatory cytokines expression at 24 h post-reperfusion. (A) TNF-α and IL-1β in cerebral ischemic penumbra determined by ELISA. Data are presented as mean ±SEM. (*p<0.05 vs. I/R+ vehicle control group). (B) The number of activated astrocytes and microglia increased after transfection with PPARγ siRNA. Scale bar=75 μm. 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: To investigate the role of PPARr in the VNS-mediated anti-inflammatory effect at the acute phase of cerebral I/R, ELISA was used to measure pro-inflammatory cytokine (TNF-α, IL-1β,) levels at 24 h post-I/R. As shown in Figure 4, results indicated that the levels of CNS inflammatory cytokines were downregulated in I/R+VNS+LV-control group than in I/R+LV-control group (p<0.05), supporting the idea that the neuroprotection induced by VNS is at least partly associated with a reduction in CNS inflammatory response. However, no significant differences in proinflammatory cytokine expression was shown I/R+VNS+LV-shPPARr and I/R +LV-shPPARr groups.


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)

The level of pro-inflammatory cytokines expression at 24 h post-reperfusion. (A) TNF-α and IL-1β in cerebral ischemic penumbra determined by ELISA. Data are presented as mean ±SEM. (*p<0.05 vs. I/R+ vehicle control group). (B) The number of activated astrocytes and microglia increased after transfection with PPARγ siRNA. Scale bar=75 μm. 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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4310716&req=5

f4-medscimonit-21-268: The level of pro-inflammatory cytokines expression at 24 h post-reperfusion. (A) TNF-α and IL-1β in cerebral ischemic penumbra determined by ELISA. Data are presented as mean ±SEM. (*p<0.05 vs. I/R+ vehicle control group). (B) The number of activated astrocytes and microglia increased after transfection with PPARγ siRNA. Scale bar=75 μm. 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: To investigate the role of PPARr in the VNS-mediated anti-inflammatory effect at the acute phase of cerebral I/R, ELISA was used to measure pro-inflammatory cytokine (TNF-α, IL-1β,) levels at 24 h post-I/R. As shown in Figure 4, results indicated that the levels of CNS inflammatory cytokines were downregulated in I/R+VNS+LV-control group than in I/R+LV-control group (p<0.05), supporting the idea that the neuroprotection induced by VNS is at least partly associated with a reduction in CNS inflammatory response. However, no significant differences in proinflammatory cytokine expression was shown I/R+VNS+LV-shPPARr and I/R +LV-shPPARr groups.

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