Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 126, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2023.111215
Keywords
AQP4; POCD; MMP-9; beta-DG; Polarity
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GM6001 alleviates postoperative cognitive deficits and neuroinflammation, preserves blood-brain barrier integrity, and rescues aquaporin-4 mislocalization. MMP-9 inhibition plays a dual role in cognitive protection through direct anti-neuroinflammatory effects and regulation of aquaporin-4 membrane distribution.
Postoperative cognitive dysfunction (POCD) is a common complication after surgery, characterized by deficits in memory, attention and cognitive flexibility. However, the underlying mechanisms of POCD remain unclear. Neuroinflammation and blood-brain barrier disruption have been implicated as potential pathological processes. This study explores the neuroprotective effects and mechanisms of the matrix metalloproteinase(MMP-9)inhibitor GM6001 against POCD. We hypothesize GM6001 may reduce neuroinflammation and preserve blood- brain barrier integrity through direct inhibition of MMP-9. Moreover, GM6001 may stabilize aquaporin-4 polarity and glymphatic clearance function by modulating MMP-9-mediated cleavage of dystroglycan, a key protein for aquaporin-4 anchoring. Our results demonstrate GM6001 alleviates postoperative cognitive deficits and neuroinflammation. GM6001 also preserves blood-brain barrier integrity and rescues aquaporin-4 mislocalization after surgery. This study reveals a novel dual role for MMP-9 inhibition in cognitive protection through direct anti-neuroinflammatory effects and regulating aquaporin-4 membrane distribution. Targeting MMP-9 may represent a promising strategy to prevent postoperative cognitive dysfunction by integrating multiple protective mechanisms.
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