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.
Cerebral hypoxia-ischemia (HI) and associated inflammation is a profound neurological problem in neonatal infants leading to poor behavioral outcomes. This proposal will advance public health and student training by evaluating critical factors of maturation and early experience that can moderate long-term behavioral outcomes in the context of novel anti-inflammatory treatment following neonatal HI injury.
|Threlkeld, Steven W; Gaudet, Cynthia M; La Rue, Molly E et al. (2014) Effects of inter-alpha inhibitor proteins on neonatal brain injury: Age, task and treatment dependent neurobehavioral outcomes. Exp Neurol 261:424-33|