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5'-adenosine monophosphate-induced hypothermia attenuates brain ischemia/reperfusion injury in a rat model by inhibiting the inflammatory response.

Miao YF, Wu H, Yang SF, Dai J, Qiu YM, Tao ZY, Zhang XH - Mediators Inflamm. (2015)

Bottom Line: Hypothermia treatment is a promising therapeutic strategy for brain injury.Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls.AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Ren Ji Hospital, South Campus, Shanghai Jiao Tong University School of Medicine, Shanghai 201112, China.

ABSTRACT
Hypothermia treatment is a promising therapeutic strategy for brain injury. We previously demonstrated that 5'-adenosine monophosphate (5'-AMP), a ribonucleic acid nucleotide, produces reversible deep hypothermia in rats when the ambient temperature is appropriately controlled. Thus, we hypothesized that 5'-AMP-induced hypothermia (AIH) may attenuate brain ischemia/reperfusion injury. Transient cerebral ischemia was induced by using the middle cerebral artery occlusion (MCAO) model in rats. Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls. AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells. The overall infarct volume was significantly smaller in AIH-treated rats, and neurological function was improved. By contrast, rats with ischemic brain injury that were administered 5'-AMP without inducing hypothermia had ischemia/reperfusion injuries similar to those in euthermic controls. Thus, the neuroprotective effects of AIH were primarily related to hypothermia.

No MeSH data available.


Related in: MedlinePlus

AIH decreases levels of neutrophil elastase expression in the infarcted brain. Coronal sections 24 h after operation were stained with specific antibodies: neutrophil elastase (green) and NeuN (red). The mounting medium contained DAPI, which counterstained the nuclei (blue). The merged images show the coexpression of NeuN and neutrophil elastase in yellow (a–e). Scale bar = 100 μm. (f) Neutrophil elastase-positive cells were quantitatively analyzed using ImageJ software. All values are the mean ± SEM. *P < 0.05 compared to the MCAO group, #P < 0.05 compared to the NT group, and &P < 0.05 compared to the HT(0.5) group.
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fig5: AIH decreases levels of neutrophil elastase expression in the infarcted brain. Coronal sections 24 h after operation were stained with specific antibodies: neutrophil elastase (green) and NeuN (red). The mounting medium contained DAPI, which counterstained the nuclei (blue). The merged images show the coexpression of NeuN and neutrophil elastase in yellow (a–e). Scale bar = 100 μm. (f) Neutrophil elastase-positive cells were quantitatively analyzed using ImageJ software. All values are the mean ± SEM. *P < 0.05 compared to the MCAO group, #P < 0.05 compared to the NT group, and &P < 0.05 compared to the HT(0.5) group.

Mentions: Ischemia/reperfusion injury is typically associated with increased inflammation. Sometime the level of neutrophil elastase expression in the infarct area is an indicator of inflammation. Immunofluorescence staining using rat neutrophil-specific antibodies was used to detect neutrophil elastase infiltration in all groups. The results indicated that there were few neutrophil elastases expressions in the sham group (Figure 5(a)). In the MCAO control group we found significant upregulation of neutrophil elastases expression in the neuronal cells in the infarcted brain area (Figure 5(b)). The NT group, which was administered 5′-AMP but maintained at a Tb in the euthermic range, exhibited a level of neutrophil elastases similar to that observed in the MCAO control group (Figure 5(c)). The same level of neutrophil elastases was also observed in the HT(0.5) group (Figure 5(e)). Only the HT(1.0) group exhibited significantly decreased levels of neutrophil elastases expression in the neuronal cells in the infarcted brain region (Figure 5(d)). Further quantitative analysis indicated that AIH treatment significantly inhibited neutrophil elastases expression in the neuronal cells in the infarcted brain area compared to the MCAO, NT, and HT(0.5) groups (P < 0.05, Figure 5(f)).


5'-adenosine monophosphate-induced hypothermia attenuates brain ischemia/reperfusion injury in a rat model by inhibiting the inflammatory response.

Miao YF, Wu H, Yang SF, Dai J, Qiu YM, Tao ZY, Zhang XH - Mediators Inflamm. (2015)

AIH decreases levels of neutrophil elastase expression in the infarcted brain. Coronal sections 24 h after operation were stained with specific antibodies: neutrophil elastase (green) and NeuN (red). The mounting medium contained DAPI, which counterstained the nuclei (blue). The merged images show the coexpression of NeuN and neutrophil elastase in yellow (a–e). Scale bar = 100 μm. (f) Neutrophil elastase-positive cells were quantitatively analyzed using ImageJ software. All values are the mean ± SEM. *P < 0.05 compared to the MCAO group, #P < 0.05 compared to the NT group, and &P < 0.05 compared to the HT(0.5) group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig5: AIH decreases levels of neutrophil elastase expression in the infarcted brain. Coronal sections 24 h after operation were stained with specific antibodies: neutrophil elastase (green) and NeuN (red). The mounting medium contained DAPI, which counterstained the nuclei (blue). The merged images show the coexpression of NeuN and neutrophil elastase in yellow (a–e). Scale bar = 100 μm. (f) Neutrophil elastase-positive cells were quantitatively analyzed using ImageJ software. All values are the mean ± SEM. *P < 0.05 compared to the MCAO group, #P < 0.05 compared to the NT group, and &P < 0.05 compared to the HT(0.5) group.
Mentions: Ischemia/reperfusion injury is typically associated with increased inflammation. Sometime the level of neutrophil elastase expression in the infarct area is an indicator of inflammation. Immunofluorescence staining using rat neutrophil-specific antibodies was used to detect neutrophil elastase infiltration in all groups. The results indicated that there were few neutrophil elastases expressions in the sham group (Figure 5(a)). In the MCAO control group we found significant upregulation of neutrophil elastases expression in the neuronal cells in the infarcted brain area (Figure 5(b)). The NT group, which was administered 5′-AMP but maintained at a Tb in the euthermic range, exhibited a level of neutrophil elastases similar to that observed in the MCAO control group (Figure 5(c)). The same level of neutrophil elastases was also observed in the HT(0.5) group (Figure 5(e)). Only the HT(1.0) group exhibited significantly decreased levels of neutrophil elastases expression in the neuronal cells in the infarcted brain region (Figure 5(d)). Further quantitative analysis indicated that AIH treatment significantly inhibited neutrophil elastases expression in the neuronal cells in the infarcted brain area compared to the MCAO, NT, and HT(0.5) groups (P < 0.05, Figure 5(f)).

Bottom Line: Hypothermia treatment is a promising therapeutic strategy for brain injury.Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls.AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Ren Ji Hospital, South Campus, Shanghai Jiao Tong University School of Medicine, Shanghai 201112, China.

ABSTRACT
Hypothermia treatment is a promising therapeutic strategy for brain injury. We previously demonstrated that 5'-adenosine monophosphate (5'-AMP), a ribonucleic acid nucleotide, produces reversible deep hypothermia in rats when the ambient temperature is appropriately controlled. Thus, we hypothesized that 5'-AMP-induced hypothermia (AIH) may attenuate brain ischemia/reperfusion injury. Transient cerebral ischemia was induced by using the middle cerebral artery occlusion (MCAO) model in rats. Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls. AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells. The overall infarct volume was significantly smaller in AIH-treated rats, and neurological function was improved. By contrast, rats with ischemic brain injury that were administered 5'-AMP without inducing hypothermia had ischemia/reperfusion injuries similar to those in euthermic controls. Thus, the neuroprotective effects of AIH were primarily related to hypothermia.

No MeSH data available.


Related in: MedlinePlus