Diabetes impairs the microglial response to cerebral microbleeds

• Main Author: Taylor, Stephanie
• Other Authors: Brown, Craig E. (Craig Edward)
• Language: English; en
• Published: 2017
• Subjects: Diabetes; Microglia; Cerebral microbleeds
• Online Access: http://hdl.handle.net/1828/7758

Approximately 7 – 9 % of the population is living with some form of diabetes. When poorly controlled (which is often the case), this disease is associated with cerebrovascular pathology such as microbleeds and impairments in cognitive function. The presence and burden of microbleeds in the brain has been strongly linked with cognitive decline and increased risk of dementia. Microglia, the resident immune cells of the central nervous system, dynamically respond to vascular insults by extending their processes to the site of injury. The rapid actions of microglia are thought to play a beneficial role in vascular repair since inhibiting these responses can exacerbate injury. Here, we hypothesized that diabetes, especially if not well controlled with insulin, will disrupt microglia responses to damaged microvessels in the brain which will lead to increased plasma leakage from damaged microvessels. Using two-photon in vivo imaging, we show that chronic hyperglycemia in the streptozotocin model of type one diabetes leads to decreased microglial process accumulation around the site of microvascular injury and increased permeability of fluorescent dyes from the damaged vessel 30 minutes after induction of the bleed. Importantly, this impaired microglial and vascular response could be partially mitigated with tight control of blood glucose levels with insulin. These results indicate that chronic hyperglycemia disrupts microglial based repair of damaged microvessels, which may help explain why poorly controlled diabetes is associated with greater a risk of cerebrovascular dysfunction and cognitive decline. === Graduate === 2018-01-12