Plasma Kallikrein and Neuroinflammation in Diabetes

Abstract

Background: One of the biggest health problems in the world is diabetes mellitus affecting 537 million people worldwide. It is subdivided into 4 chronic disorders, one of which is Type 1 Diabetes (T1D) characterized by β-cells destruction, resulting in hyperglycemia. The increase in blood glucose levels has different micro-complications including neuropathy and retinopathy thus causing cognitive dysfunction. As a consequence, when an individual begins to experience vision loss, reduced peripheral sensation, and cognitive decline, their risk of falling and injuring their heads increases. Thus, traumatic brain injuries (TBI) become more prevalent among these individuals. TBI can provoke the onset of many neurological and psychological problems. Further understanding of the mechanisms of neuroinflammation post-TBI is needed to address these problems. The maestro of neuroinflammation in the CNS is microglial cells. They are the residential macrophages of the brain, and have key functions in the neuroimmune response and in regeneration. In our previous work, we showed that Plasma Kallikrein system (PKall) holds significant importance in activating and regulating microglia. It facilitates the production and dissemination of inflammatory mediators, thereby contributing to the progression of neurodegenerative disorders. Aims: The aim of this study is to determine the mechanism by which PKall activates microglial cells in a diabetic mouse model following TBI. Methods: C57BL/6J mice were injected with streptozotocin to induce T1D. Once hyperglycemia was achieved, TBI was performed on the right parietal cortex. Our control group is the diabetic SHAM mice. Levels of blood glucose and weight is reported. From the isolated plasma, we will assess the PKall protein levels. Additionally, inflammatory biomarkers in the parietal cortex of the brain will be analyzed at transcriptomic levels. Conclusion: Our preliminary data showed that PKall is upregulated in the plasma of TBI mice versus SHAM. This study will contribute to establish the mechanism through which PKall modulates neuroinflammation. This will enhance our comprehension of neurodegenerative disease development and prevention.