Background Sterile inflammation resulting from myocardial injury activates the NLRP3 inflammasome and amplifies the inflammatory response mediating further damage. Methods We used two experimental models of ischemic injury (acute myocardial infarction [AMI] with and without reperfusion) and a model of non-ischemic injury due to doxorubicin 10 mg/Kg, to determine whether the NLRP3 inflammasome preserved cardiac function after injury. Results Treatment with the NLRP3 inflammasome inhibitor in the reperfused AMI model caused a significant reduction in infarct size measured at pathology or as serum cardiac troponin I level (−56% and −82% respectively, both p<0.001), and preserved LV fractional shortening (LVFS, 31±2 vs vehicle 26±1%, p=0.003). In the non-reperfused AMI model treatment with the NLRP3 inhibitor significantly limited LV systolic dysfunction at 7 days (LVFS of 20±2 vs 14±1%, p=0.002), without a significant effect on infarct size. In the DOX model, a significant increase in myocardial interstitial fibrosis and a decline in systolic function were seen in vehicle-treated mice, whereas treatment with the NLRP3 inhibitor significantly reduced fibrosis (−80%, p=0.001) and preserved systolic function (LVFS 35±2 vs vehicle 27±2%, p=0.017). Conclusion Pharmacological inhibition of the NLRP3 inflammasome limits cell death and LV systolic dysfunction following ischemic and non-ischemic injury in the mouse.

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A recombinant retrovirus vector containing the glial cell line-derived neurotrophic factor (GDNF) gene was constructed and transfected into Schwann cells (SCs) to investigate the possibility of GDNF transfection and functional expression of transfected SCs, including GDNF secretion and its mRNA expression. We found that transfection of the GDNF gene into SCs led to significantly enhanced expression of GDNF mRNA. The rate of GDNF secretion by GDNF-SCs was also increased. Functionally, more surviving motoneurons were seen when they were cocultured in GDNF-SC-conditioned medium than when they were in normal SC-conditioned medium. When bridging a rat sciatic nerve defect with a conduit filled with GDNF-transfected SCs, nerve regeneration was better than that of the control. In conclusion, transfection of SCs with the GDNF gene could enhance SC function. Application of genetically modified SCs could be a better way to promote nerve regeneration.

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