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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 reduces MMP-9, IL-1R, TNFR, and TLR protein levels in the infarcted brain. (a) Western blot analysis of protein expression of MMP-9, IL-1R, TNFR, and TLR in the sham, MCAO, NT, HT(1.0), and HT(0.5) groups. β-Actin was used as an internal reference. (b) Optical density analysis of MMP-9, IL-1R, TNFR, and TLR. 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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fig6: AIH reduces MMP-9, IL-1R, TNFR, and TLR protein levels in the infarcted brain. (a) Western blot analysis of protein expression of MMP-9, IL-1R, TNFR, and TLR in the sham, MCAO, NT, HT(1.0), and HT(0.5) groups. β-Actin was used as an internal reference. (b) Optical density analysis of MMP-9, IL-1R, TNFR, and TLR. 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: Western blot analysis was performed to detect the levels of the inflammation-related proteins MMP-9, IL-1R, TNFR, and TLR. As with neutrophil infiltration, the MMP-9, IL-1R, TNFR, and TLR protein levels were increased in the MCAO control group and the NT group (Figure 6(a)). The dose of 0.5 mg 5′-AMP/g body weight also did not reduce the MMP-9, IL-1R, TNFR, and TLR levels (Figure 6(a)). A greater reduction of MMP-9, IL-1R, TNFR, and TLR expression was observed in the 1.0 mg 5′-AMP/g body weight treatment group (Figure 6(a)). To confirm this observation, β-actin levels were used as an internal reference for quantitative analysis. These data indicate that AIH treatment significantly reduced MMP-9, IL-1R, TNFR, and TLR protein levels in the infarcted brain area compared to the MCAO, NT, and HT(0.5) groups (P < 0.05, Figure 6(b)).


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 reduces MMP-9, IL-1R, TNFR, and TLR protein levels in the infarcted brain. (a) Western blot analysis of protein expression of MMP-9, IL-1R, TNFR, and TLR in the sham, MCAO, NT, HT(1.0), and HT(0.5) groups. β-Actin was used as an internal reference. (b) Optical density analysis of MMP-9, IL-1R, TNFR, and TLR. 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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getmorefigures.php?uid=PMC4385688&req=5

fig6: AIH reduces MMP-9, IL-1R, TNFR, and TLR protein levels in the infarcted brain. (a) Western blot analysis of protein expression of MMP-9, IL-1R, TNFR, and TLR in the sham, MCAO, NT, HT(1.0), and HT(0.5) groups. β-Actin was used as an internal reference. (b) Optical density analysis of MMP-9, IL-1R, TNFR, and TLR. 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: Western blot analysis was performed to detect the levels of the inflammation-related proteins MMP-9, IL-1R, TNFR, and TLR. As with neutrophil infiltration, the MMP-9, IL-1R, TNFR, and TLR protein levels were increased in the MCAO control group and the NT group (Figure 6(a)). The dose of 0.5 mg 5′-AMP/g body weight also did not reduce the MMP-9, IL-1R, TNFR, and TLR levels (Figure 6(a)). A greater reduction of MMP-9, IL-1R, TNFR, and TLR expression was observed in the 1.0 mg 5′-AMP/g body weight treatment group (Figure 6(a)). To confirm this observation, β-actin levels were used as an internal reference for quantitative analysis. These data indicate that AIH treatment significantly reduced MMP-9, IL-1R, TNFR, and TLR protein levels in the infarcted brain area compared to the MCAO, NT, and HT(0.5) groups (P < 0.05, Figure 6(b)).

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