Anti-RAGE antibody attenuates isoflurane-induced cognitive dysfunction in aged rats

Area of Science:

• Neuroscience
• Anesthesiology
• Pharmacology

Background:

• Volatile anesthetics like isoflurane can impair blood-brain barrier (BBB) integrity, leading to cognitive deficits.
• Receptor for advanced glycation end-products (RAGE) is crucial for maintaining BBB integrity.
• The role of RAGE in isoflurane-induced BBB disruption and cognitive impairment requires further investigation.

Purpose of the Study:

• To investigate if a RAGE-specific antibody can protect against isoflurane-induced BBB disruption and cognitive impairment in aged rats.

Main Methods:

• 108 aged rats were divided into control, isoflurane (ISO), RAGE antibody + ISO (anti-RAGE+ISO), and RAGE antibody (anti-RAGE) groups.
• Isoflurane exposure involved 4 hours of 2% concentration.
• RAGE antibody treatment involved 20μL at 2.5μg/μL.
• Assessments included hippocampal RAGE expression, BBB integrity, neuroinflammation, beta-amyloid (Aβ) accumulation, and cognitive function via Morris water maze.

Main Results:

• Isoflurane anesthesia upregulated hippocampal RAGE, disrupted BBB integrity, increased neuroinflammation, and promoted Aβ accumulation in aged rats.
• Isoflurane exposure led to significant cognitive deficits in the Morris water maze test.
• RAGE antibody pretreatment significantly improved BBB integrity, attenuated RAGE expression, neuroinflammation, and Aβ accumulation.
• Antibody administration mitigated isoflurane-induced cognitive impairment.

Conclusions:

• RAGE signaling is critically involved in the blood-brain barrier damage and cognitive impairment induced by isoflurane exposure.
• RAGE-specific antibodies represent a potential therapeutic strategy to prevent anesthesia-related cognitive dysfunction.