Effect of GLP-1R Knockout on stroke outcome

Abstract: Stroke is the leading cause of disability in adults in westernized societies and it has an important impact on health and economy. Comorbid health conditions such as hypertension, inactive lifestyle, smoking, obesity and diabetes considerably increase the risk of stroke. Moreover, studies have shown an increased probability of stroke occurrence and recurrence in the type 2 diabetes (T2D). Stroke leads to neurological deficits like motor impairments, disabilities and poor quality of life. The need of finding a novel treatment that can assure neuroprotective effects is crucial considering that the incidence of T2D is increasing around the world. Thrombolytic treatment given within 3-4 h from the stroke can assure some protection. Unfortunately, too few patients can benefit of this treatment due to a delayed arrival at the hospital, incorrect diagnoses or other causes. Furthermore, drugs that have shown some neuroprotective effectiveness in the pre-clinical experiments, failed in the clinical trials and today, there is no treatment for stroke based on neuroprotection. Glucagon-like peptide 1 (GLP-1) is a peptide found in L-cells of the small intestine and is secreted after the meal. The activation of its receptor (GLP-1R) increases the glucose-dependent insulin secretion and decreases the glucagon secretion. Exendin-4 (Ex-4) is a GLP-1R agonist that showed efficacy against stroke in diabetes in animal models. Additionally, it has been demonstrated that Ex-4 is acting through the activation of GLP-1R. The aim of the present study was to determine if the receptor itself plays a role in stroke outcome (without Ex-4) and see if the stroke-induced inflammation is affected by the lack of GLP-1R. We compared knockout vs. wild type mice by evaluating the stroke volume and by performing stereological counting of neurons in the striatum and cortex. The results showed no significant differences between the two groups, indicating that the lack of GLP-1R plays no role in stroke outcome.