Steven Wakely Threlkeld, Ph.D. - US grants

DESCRIPTION (provided by applicant): Developmental brain injury, resulting from reduced blood oxygenation and blood flow (c), persists as one of the most pressing neurological problems in the perinatal period. In a significant number of cases these insults lead to language and other severe cognitive deficits (e.g., working memory). However, current treatment and prevention strategies are inadequate and assessments of experiential therapies, while essential, are often confined to cellular outcome. Evidence from our group indicates that early anti- inflammatory intervention (Inter-alpha-Inhibitor Protein (IAIP)) and early behavioral training significantly improve later behavioral performance in rodent models of developmental brain injury. Further, research has shown maturation related behavioral improvements in adult animals with early developmental brain injury as compared to juveniles. However, no studies have systematically evaluated the relative benefits of both early domain specific behavioral intervention and prophylactic treatments in relation to maturation. The aim of this proposal is to assess the relative influences of anti-inflammatory intervention with inter-alpha-inhibitor protein early domain specific behavioral experience (auditory processing or working memory), and maturation on adult behavioral and anatomical outcomes in a rodent model of perinatal brain injury. Understanding the relative benefits of both early-targeted behavioral intervention and anti-inflammatory treatments, in relation to maturation, will have profound implications for early mediation strategies in high-risk neonatal populations. Finally, this proposal will enhance student opportunities at Rhode Island College by increasing neurobehavioral research resources, funding summer student research and enhancing undergraduate research training.

Project Summary: 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.