Insulin and Brain Injury: Memory, Metabolism and Microglia
Abstract
Traumatic brain injury (TBI) may result in long term learning and memory dysfunction. The cognitive deficits are the result of cellular and metabolic dysfunction that occurs after injury, including neuronal cell death, decreased cerebral glucose uptake and inflammation. To date, no therapeutic intervention has successfully addressed these post injury deficits. The goals of this study were to provide insight into the mechanism of post-injury cerebral metabolism, assess the ability of intranasal insulin to increase cerebral glucose uptake, memory and learning function after injury, and examine insulins effect on microglia mediated inflammation. Adult male Sprague Dawley rats were exposed to a moderate controlled cortical impact (CCI) injury or isoflurane and were sacrificed at 24 hours post procedure. The protein levels of glucose transporters (GLUTs) 1, 3, and 4 as well as insulin receptor (IR) were examined in the cortex, hippocampus, and cerebellum. No significant change in IR or GLUT expression was observed in the ipsilateral cortex hippocampus, or cerebellum at 24 hours post injury compared to uninjured controls. To further examine the role of insulin after TBI, adult male Sprague Dawley rats were exposed to a moderate controlled cortical impact (CCI) injury followed by intranasal insulin or saline treatment beginning 4 hours post-injury and continuing with daily administration for 14 days. Positron emission tomography (PET) of fluorodeoxyglucose ([18F]-FDG) uptake was performed prior to injury and at 48 hours and 10 days post-injury. Motor function was tested using the beam and peg board walking test. Learning and memory function was assessed using the Morris water maze. Tissue was collected for assessment of macrophage and astrocyte activity.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 20, 2016
- Accession Number
- AD1036442
Entities
People
- Fiona P. Brabazon
Organizations
- Uniformed Services University of the Health Sciences