Abstract
Carbon monoxide-releasing molecule-3 (CORM-3), which is an exogenous carbon monoxide (CO) compound, slowly releases CO under physiological conditions; this exerts neuroprotective effects against incomplete ischemia/reperfusion injury. The objective of the present study was to investigate whether the administration of CORM-3 protects against nucleotide-binding oligomerization domain-like receptor pyrin domain-3 (NLRP3) inflammasome formation and neuronal pyroptosis in the hippocampus following hemorrhagic shock and resuscitation (HSR). To establish this, an HSR model was created. Hemorrhagic shock was induced in adult male Sprague-Dawley rats under sevoflurane anesthesia by bleeding using a heparinized syringe to maintain a mean arterial pressure of 30±5 mmHg for 60 min. Resuscitation was performed by reperfusion of the blood and, if necessary, administering sterile saline to achieve the baseline arterial pressure. Following resuscitation, CORM-3 (4 mg/kg) was injected via the femoral vein. Neuronal pyroptosis in the hippocampus, mitochondrial morphology, mitochondrial DNA (mtDNA), brain magnetic resonance imaging, expression levels of NLRP3 and the interaction of pro-caspase-1 and apoptosis-associated speck-like protein containing a CARD domain (ASC) were examined 12 h after HSR; locomotor activity was assessed 7 days after HSR. Compared with HSR-treated rats, CORM-3 administration resulted in a lower level of neuronal pyroptosis in the hippocampus, improved mitochondrial morphology, a lower mtDNA level, steadier levels of metabolites, decreased expression levels of NLRP3 and pro-caspase-1 interacting with ASC and enhanced locomotor activity. In conclusion, treatment with CORM-3 ameliorated impairments of locomotor and exploratory activities in a rat model of HSR. The mechanism may be associated with the inhibition of mitochondrial DNA-induced pyroptosis via improvements in cell metabolism.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
