Neurologic Deficit Score at 4-5 Days Post-eCPR Predicts Long-Term Brain Dysfunction in Rats Following Cardiac Arrest

Area of Science:

• Neuroscience
• Cardiology
• Biochemistry

Background:

• Cardiac arrest (CA) survivors frequently experience long-term neurological deficits.
• The impact of CA on specific brain regions and neurological outcomes requires further investigation.
• Heme oxygenase (HO) activity in the hippocampus and cortex was previously identified as a potential functional outcome marker post-CA.

Purpose of the Study:

• To investigate the long-term neurological outcomes and brain region-specific changes following cardiac arrest (CA) and extracorporeal cardiopulmonary resuscitation (ECPR).
• To assess the correlation between early neurological deficit scoring (NDS) and delayed enzymatic dysfunction in the hippocampus.
• To identify potential therapeutic intervention windows post-CA.

Main Methods:

• A rat model of CA was established with varying durations (6 or 8 minutes) followed by ECPR.
• Neurological impairment was assessed daily using neurologic deficit scoring (NDS).
• Neuroinflammatory, neurodegenerative markers, and enzyme activities (HO, 2-oxoglutarate dehydrogenase complex) were measured in brain tissue 14 days post-CA.

Main Results:

• Survival rates were 67% for 6-min CA and 33% for 8-min CA by day 14 post-ROSC.
• The 8-min CA group exhibited significantly worse neurological outcomes compared to the 6-min group until day 14.
• Elevated neuroinflammatory markers (HO-1, TNF-R1, Iba1, GFAP) and reduced HO and 2-oxoglutarate dehydrogenase complex activities were observed in the hippocampus.
• NDS at days 4-5 strongly correlated with delayed CA-mediated enzymatic dysfunction in the hippocampus.

Conclusions:

• Neurological deficits persist long after cardiac arrest, with severity dependent on CA duration.
• Early neurological deficit scoring (NDS) at 4-5 days post-CA can predict delayed enzymatic dysfunction in the hippocampus.
• Therapeutic interventions may need to be prolonged, extending at least to 4 days post-CA, to address these persistent deficits.