Abstract TP252: Intranasal Insulin Treatment Improves Stroke Outcome In Both Male And Female Mice

Abstract

Insulin resistance has been linked to increased risk of stroke recurrence, death, and poor outcome following stroke. Insulin resistance, a common phenomenon following stroke, is associated with elevated levels of insulin circulating in the periphery, which leads to brain insulin deficiency. Brain insulin promotes neuroplasticity and synaptogenesis, has anti-inflammatory, anti-thrombotic, vasodilatory, and anti-apoptotic properties. The impact of brain insulin deficiency and the therapeutic potential of increasing brain insulin levels has yet to be fully understood. Hence, purpose of this study is to assess the potential therapeutic benefits of intranasal insulin treatment on stroke outcomes in a mouse model of brain insulin deficiency. Ischemic stroke was induced using a 30 minute middle cerebral artery occlusion (MCAO) in 16 week old (12 week diet) male and female mice on either a standard diet (control) or a high-fat diet induced at 4 weeks of age, a model of brain insulin deficiency. Recovery assessments begin on day 0 following stroke and continue until day 14 post stroke. Recovery assessments entail observing survival, neurological, motor, and cognitive function after receiving either intranasal saline (0.9%) or intranasal insulin (1.75 U). These assessments were evaluated by survival, and completion of the neurological severity score, ladder, and problem solving tasks on days 0-14 post stroke. High-fat diet-induced brain insulin deficiency was associated with worse survival and neurological deficits following ischemic stroke, intranasal insulin improved stroke mortality and neurological assessments in high-fat diet mice. Thus, intranasal insulin may be a useful therapy for improving stroke outcomes.

The need for registry‐based studies in diabetes and stroke: A unique opportunity to understand whether diabetic treatments improve post‐stroke outcome

“…7 Moreover, it was recently shown that the administration of insulin intranasally could treat brain insulin deficiency in high-fat diet-fed insulin-resistant mice as well as improve their post-stroke cognitive function. 8 The biguanide metformin is the first-line glucose-lowering treatment in people with T2D. Its main mechanism of action occurs in the liver with the blocking of gluconeogenesis, but it also acts as an insulin-sensitizer.…”