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

## TL;DR

A neurological score measured 4–5 days after resuscitation predicts long-term brain damage in rats after cardiac arrest.

## Contribution

The study identifies a specific time point for predicting brain dysfunction and suggests prolonged therapeutic intervention.

## Key findings

- Neurological deficit scores at 4–5 days post-CA correlate with delayed enzymatic dysfunction in the hippocampus.
- Rats with 8 minutes of CA showed worse neurological outcomes and higher mortality compared to those with 6 minutes.
- Reduced HO activity and elevated neuroinflammatory markers indicate impaired anti-oxidative and mitochondrial functions.

## Abstract

Cardiac arrest (CA) survivors often develop long-term neurological deficits, but its long-term impact on vulnerable brain regions and neurological outcomes remains unclear. In a previous CA model with conventional cardiopulmonary resuscitation, we found reduced heme oxygenase (HO) activity in the hippocampus and cortex 14 days post-CA, suggesting its potential as a functional outcome marker. Here, we used a rat model with 6 or 8 min of CA followed by extracorporeal cardiopulmonary resuscitation. While in the 6 min-CA group, 67% survived to day 14, increased mortality within 4 days resulted in only 33% survival in the 8 min group post-ROSC. All animals displayed neurological impairment assessed by daily neurologic deficit scoring (NDS). While deficits declined within the first 3–4 days in the 6 min-CA animals, the 8 min-CA group showed significantly worse neurological outcomes until day 14. Two weeks post-CA, neuroinflammatory and neurodegenerative markers (HO-1, TNF-R1, Iba1, and GFAP) were elevated in the hippocampus, while HO and 2-oxoglutarate dehydrogenase complex activities were reduced in all rats, indicating a decrease in anti-oxidative capacity and mitochondrial capacity for metabolizing glutamate. NDS at day 4–5 strongly correlated with the delayed CA-mediated enzymatic dysfunction determined in the hippocampus. This finding highlights this time point for identifying at-risk individuals and suggests a prolonged therapeutic intervention lasting at least until 4 days post-CA.