This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Traumatic injury to the nervous system (brain, spinal cord, and nerves) occurs with increasing regularity in children causing an enormous amount of death, pain, disability and financial hardship. For example over 1,000,000 children each year sustain mild to severe brain injuries with estimates that over 30,000 result in permanent disability. Medical interventions provided in the emergency room and later in rehabilitation to treat 'neurotrauma' have proven to be only moderately successful leading to a call for new research to address these issues. Knowledge of genes (DNA), the design templates on which our bodies are built, has increased exponentially in recent years and along with it our ability to associate these genes and their protein products with disease states or the ability to cope with injury. This study seeks to demonstrate that there is a link between the gene for Apolipoprotein E (ApoE), whose protein product facilitates the movement of fats and cholesterol throughout the body, and the ability of a child's brain and spinal cord to recover from injury. Research indicates that ApoE is important for cells within the nervous system to grow and make new connections. There are 3 different forms of ApoE which can be inherited by humans (ApoE2, 3, & 4) and each form varies in its ability to function. The ApoE4 form, found in as much as 40% (23% on average) of the population, has been associated with increased risk for Alzheimer's Disease and its presence predicts a more severe injury and poorer recovery from neurotrauma in adults. In animals, lack of ApoE also results in increased severity of injury after trauma to the nervous system and diminished capacity for learning and memory. To date, no research has been done to determine if having the E4 form of Apolipoprotein E diminishes the ability of children to recover from injury to their brain or spinal cord. This study will compare how children have recovered from brain or spinal cord injury in the past to which forms of the ApoE gene they have inherited from their parents. In addition, a more thorough evaluation of future brain/spinal cord injured children will be done to answer other related questions such as: does it make a difference if the patients are male or female, is their age upon injury important, does the severity of their injury play a role, or does it matter if the child has reached puberty? The importance of these studies lies in our ability to identify children at risk for more severe brain injuries and disability based on genetic factors. If this link can be established then a treatment option may be designed based on defects associated with these genetic influences.
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