TRPV1 modulated NLRP3 inflammasome activation via calcium in experimental subarachnoid hemorrhage.

Abstract

Neuroinflammation plays a key role in early brain injury (EBI) of subarachnoid hemorrhage (SAH), and NLRP3 inflammasome plays an important role in the development of neuroinflammation after SAH, but the mechanism of NLRP3 inflammasome activation after SAH is still unclear. TRPV1 is a non-selective calcium channel that is involved in the pathology of neuroinflammation, but its role in SAH has not been revealed. Our study showed that TRPV1 was significantly upregulated after SAH and was predominantly expressed in microglia/macrophages. Antagonism of TRPV1 was effective in ameliorating neurological impairment, brain edema, neuronal damage, and reducing the inflammatory response (evidenced by reducing the number of CD16/32 positive microglia/macrophages, inhibiting the expression of CD16, CD32, CD86, IL-1b, TNF-a and blocking NLRP3 inflammasome activation). However, this effect can be abolished by NLRP3 inflammasome antagonist MCC950. In vitro experiment confirmed that TRPV1 activated NLRP3 inflammasome by increasing intracellular calcium levels. In conclusion, TRPV1 mediates EBI after SAH via calcium/NLRP3, and TRPV1 is a potential therapeutic target after SAH.

• Authors: Keke Zhang, Zhen Qin, Jinyan Chen, Gengyin Guo, Xiaokun Jiang, Feng Wang, Jianfeng Zhuang, Zhen Zhang
• Journal: Aging (Aging (Albany NY)) Vol. 16 Issue 2 Pg. 1096-1110 (Jan 04 2024) ISSN: 1945-4589 [Electronic] United States
• PMID: 38180747 (Publication Type: Journal Article)

Chemical References

• Calcium
• Calcium, Dietary
• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein

Topics

• Animals
• Brain Injuries (drug therapy)
• Calcium (therapeutic use)
• Calcium, Dietary (therapeutic use)
• Inflammasomes (metabolism)
• Neuroinflammatory Diseases
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Rats, Sprague-Dawley
• Subarachnoid Hemorrhage (pathology)
• Mice
• Rats