Long-lasting cognitive injury in rats with apparent full gross neurological recovery after short-term cardiac arrest

Objective: The long-term behavioral effects of mild global ischemia have not been well described. We used short (5 min) asphyxic-cardiac arrest that resulted in no apparent gross neurological deficits to study the long-term effects of mild hypoxic ischemia on the neurobehavioral status of rats. Methods: Fifteen adult, male Wistar rats were studied. One group was given asphyxic-cardiac arrest (CA) for 5 min (n = 10) and the other group had Sham procedure (n = 5). Neurobehavioral testing was performed before and 2 weeks after CA. The neurobehavioral evaluations were: neurological deficit score (NDS), Y Maze, open field, pre-pulse inhibition (PPI) of acoustic startle reflex (ASR), wire hanging, and inclined screen. Results: At 24 h post-CA, all of the rats regained normal neurological function as measured by NDS, an integral score for consciousness, brainstem reflexes, sensorimotor function and simple behavioral reflex tests. However, 1 week after CA, the rats exhibited significant activity reductions in the open field and in spontaneous alternation in the Y maze. The CA rats also showed a significant decrease in startle reaction amplitude and startle inhibition in the PPI tests. Two weeks after CA, the changes in motor activity and deficits in PPI remained significant, but the spontaneous alternation recovered. The muscle strength test of wire hanging and inclined screen tests did not exhibit significant change. Conclusion: We present a rodent model of mild CA that, despite apparent full recovery of global neurological function at 24 h post-resuscitation, exhibited long-term cognitive injury lasting for at least 2 weeks after CA. This model may help understand better the injury associated with CA and develop management strategies for mild brain injury.