Altered Neural Networks in the Papez Circuit: Implications for Cognitive Dysfunction after Cerebral Ischemia

Cerebral ischemia remains a leading cause of mortality worldwide. Although the incidence of death has decreased over the years, surviving patients may suffer from long-term cognitive impairments and have an increased risk for dementia. Unfortunately, research aimed toward developing therapies that can improve cognitive outcomes following cerebral ischemia has proved difficult given the fact that little is known about the underlying processes involved. Nevertheless, mechanisms that disrupt neural network activity may provide valuable insight, since disturbances in both local and global networks in the brain have been associated with deficits in cognition. In this review, we suggest that abnormal neural dynamics within different brain networks may arise from disruptions in synaptic plasticity processes and circuitry after ischemia. This discussion primarily concerns disruptions in local network activity within the hippocampus and other extra-hippocampal components of the Papez circuit, given their role in memory processing. However, impaired synaptic plasticity processes and disruptions in structural and functional connections within the Papez circuit have important implications for alterations within the global network, as well. Although much work is required to establish this relationship, evidence thus far suggests there is a link. If pursued further, findings may lead toward a better understanding of how deficits in cognition arise, not only in cerebral ischemia, but in other neurological diseases as well.