Adiponectin reduces brain injury after intracerebral hemorrhage by reducing NLRP3 inflammasome expression

Abstract

Background and Purpose: Intracerebral hemorrhage (ICH) is a severe disease without effective therapeutic means. Adiponectin (APN) is strongly expressed in human brain tissue and cerebrospinal fluid and may play an anti-inflammatory role following ICH. NLR family pyrin domain-containing protein 3 (NLRP3) is a member of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family. Following ICH, activation of the NLRP3 inflammasome promotes neuroinflammation and brain edema. Here, we examined the effect of APN and the NLRP3 inflammasome on brain injury in an autologous blood model of ICH in rats and assessed whether APN could provide neuroprotection against inflammation by inhibiting NLRP3 activity.

Methods: The ICH model was produced by injection of 50 μl fresh autologous blood into brain, we used lentiviral-mediated overexpression of APN to determine the efficacy and mechanism of APN therapy in ICH injury.

Results: APN decreased interleukin-1β(IL-1β) and interleukin-18 (IL-18) production, attenuated neurological deficits, and reduced perihematomal brain edema 24 h after ICH. In rats with ICH, the protective effect of APN was associated with the reduced expression of NLRP3. APN and MCC950 (an NLRP3 inhibitor) both showed the same neuroprotective effect of reducing the expression of NLRP3, IL-1β and IL-18.

Conclusions: These results indicated that APN and the NLRP3 inflammasome inhibitor, MCC950, played the similar function in reducing brain injury and improving prognosis. Although further research is needed to confirm this, our findings suggest that APN may regulate inflammation injury via NLRP3 signaling.

Keywords:

• APN
• intracerebral hemorrhage
• NLRP3
• inflammation

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by grants from Natural Science Foundation of the Sichuan Provincial Education Office (18ZA0529), Sichuan Provincial Health and Family Planning Commission Research Project (No.18PJ023 and 18PJ024), Science Foundation of Southwest Medical University (0903-00030982), The Science Foundation of the Affiliated Hospital of Southwest Medical University (2017-PT-7) and The Doctoral Scientific Research startup Fund Project of the Affiliated Hospital of Southwest Medical University.