Intranasal insulin treatment of an experimental model of moderate traumatic brain injury

Abstract

Traumatic brain injury (TBI) results in learning and memory dysfunction. Cognitive deficits result from cellular and metabolic dysfunction after injury, including decreased cerebral glucose uptake and inflammation. This study assessed the ability of intranasal insulin to increase cerebral glucose uptake after injury, reduce lesion volume, improve memory and learning function and reduce inflammation. Adult male rats received a controlled cortical impact (CCI) injury followed by intranasal insulin or saline treatment daily for 14 days. PET imaging of [18F]-FDG uptake was performed at baseline and at 48 h and 10 days post-injury and MRI on days three and nine post injury. Motor function was tested with the beam walking test. Memory function was assessed with Morris water maze. Intranasal insulin after CCI significantly improved several outcomes compared to saline. Insulin-treated animals performed better on beam walk and demonstrated significantly improved memory. A significant increase in [18F]-FDG uptake was observed in the hippocampus. Intranasal insulin also resulted in a significant decrease in hippocampus lesion volume and significantly less microglial immunolabeling in the hippocampus. These data show that intranasal insulin improves memory, increases cerebral glucose uptake and decreases neuroinflammation and hippocampal lesion volume, and may therefore be a viable therapy for TBI.

Role of Insulin in Neurotrauma and Neurodegeneration: A Review

“…Our previous work demonstrated that after a moderate TBI in rats, intranasal insulin administered within 4 h after injury significantly increased glucose uptake in the hippocampus, improved cognitive function, and reduced inflammation (Brabazon et al, 2017). In this study, insulin administered daily for 14 days significantly improved performance in a Morris water maze task as well as improved time to cross a beam during a beam walk task.…”

The effects of insulin on the inflammatory activity of BV2 microglia

“…[ 23 ] Our lab has shown a significant improvement in memory function after moderate brain injury with intranasal insulin treatment. [ 24 ] Interestingly, this improvement in memory function was correlated with a significant reduction in microglial staining in the brain after intranasal insulin treatment, similar to that observed by Chen et al[ 23 ]…”

Longitudinal Microstructural Changes in Traumatic Brain Injury in Rats: A Diffusional Kurtosis Imaging, Histology, and Behavior Study

“…In fact, previous studies have reported poorer performance on the Morris water maze tests as early as 2 weeks after TBI. [36][37][38] We speculated that persistent cortex, hippocampus, and corpus callosum abnormalities revealed by the DKI parameter changes would cause disruption of the brain cognitive network, thus leading to cognitive impairment.…”