Developmental brain injury, resulting from reduced blood oxygenation and blood flow (Hypoxia/ischemia), persists as one of the most pressing neurological problems in the perinatal period. In a significant number of cases these insults lead to working memory and other severe cognitive deficits. Although the use of behavioral intervention has increased in recent years, current treatment and prevention strategies are inadequate. Further, little is known about optimal age related cognitive intervention windows or the effects of early cognitive experience on neuronal architecture (dendritic branching patterns and spine alterations) in related brain systems that may underlie recovery. Evidence from our group indicates that combining early anti-inflammatory intervention (Inter-alpha-Inhibitor Proteins (IAIPs)) and early behavioral experience significantly improve later behavioral performance in rodent models with developmental brain injury and leads to changes in neuron structure. However, no studies have systematically evaluated the timing at which plasticity occurs or the critical age dependent windows required for brain changes that may facilitate improved outcomes following early cognitive experience.
The aim of this proposal is to assess the timing at which neuronal branch and spine level plasticity emerge after early cognitive experience and IAIPs treatment, and to identify the age window required for the combined interventions to facilitate neuronal plasticity in rats with HI injury. Understanding the relative benefits of both early-targeted cognitive intervention/experience and drug treatment, requires a determination of when plasticity is initiated after training and the optimal window for cognitive intervention. These studies will have important implications for early mediation strategies in high-risk neonatal populations. Finally, this proposal will enhance student research engagement at Regis College by increasing neurobehavioral research resources, funding student research and enhancing undergraduate research training.
Cerebral hypoxia-ischemia (HI) and associated inflammation are profound neurological problems in at-risk infants leading to poor behavioral outcomes. This project will advance public health and student training by evaluating the onset timing of neuronal plasticity after early working memory experience and the critical age window required for experience dependent plasticity in the presence of anti-inflammatory treatment following neonatal HI injury.
