Grants and Contracts Details
The incidence of spinal cord injury (SCI) among older individuals has increased in recent years. According to the Kentucky Injury Prevention and Research Center, in 2007, 61% of all non-fatal SCIs were sustained by individuals >45 years old. Aged animals have reduced rates of recovery, residual locomotor deficits, and increased areas of pathology and demyelination after SCI compared to young animals, but the mechanisms behind these age-related differences are not well understood. Macrophages are a hallmark of CNS trauma and can facilitate repair or pathology in the injured spinal cord. Age is a key regulatory of macrophage function and aging is associated with increased activation of pathological macrophage phenotypes.Thus, in the current proposal, we hypothesize that age contributes to the impairment of functional recovery following SCI by potentiating oxidative stress through alteration of NOX activity, overproduction of ROS, and subsequent changes in macrophage phenotypes. This hypothesis will be examined through the following aims: Aim 1: To study the hypothesis that age increases oxidative damage in the injured spinal cord tissue via alteration of NOX activity. Aim 2: To study the hypothesis that age-induced overproduction of ROS is associated with changes in macrophage phenotype, which further contribute to the proinflammatory responses and tissue damage following SCI. There are only few published basic science reports examining pathology and secondary injury mechanisms after SCI in aged animals. Therefore, completion of these experiments will provide valuable, informative data for the SCI field about a growing, but understudied, population of aged individuals sustaining SCI. Understanding how age alters the microenvironment of the spinal cord and macrophage activation will help define strategies to promote therapeutic interventions, especially in individuals injured later in life.
|Effective start/end date||7/1/14 → 3/31/17|
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