NLRP3 Inflammasome Inhibition with MCC950 Improves Diabetes-Mediated Cognitive Impairment and Vasoneuronal Remodeling After Ischemia

Publication date: Available online 25 February 2019Source: Pharmacological ResearchAuthor(s): Rebecca Ward, Weiguo Li, Yasir Abdul, LaDonya Jackson, Guangkuo Dong, Sarah Jamil, Jessica Filosa, Susan C. Fagan, Adviye ErgulAbstractDiabetes increases the risk and worsens the progression of cognitive impairment via the greater occurrence of small vessel disease and stroke. Yet, the underlying mechanisms are not fully understood. It is now accepted that cardiovascular health is critical for brain health and any neurorestorative approaches to prevent/delay cognitive deficits should target the conceptual neurovascular unit (NVU) rather than neurons alone. We have recently shown that there is augmented hippocampal NVU remodeling after a remote ischemic injury in diabetes. NLRP3 inflammasome signaling has been implicated in the development of diabetes and neurodegenerative diseases, but little is known about the impact of NLRP3 activation on functional and structural interaction within the NVU of hippocampus, a critical part of the brain that is involved in forming, organizing, and storing memories. Endothelial cells are at the center of the NVU and produce trophic factors such as brain derived neurotrophic factor (BDNF) contributing to neuronal survival, known as vasotrophic coupling. Therefore, the aims of this study focused on two hypotheses: 1) diabetes negatively impacts hippocampal NVU remodeling and worsens cognitive outcome after stroke, and 2) NLRP3 inhibition with MCC950 wil...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research