Metabolik hastalıklarda perisitlerin rolü

Type-1 diabetes (T1DM), type-2 diabetes and hypertension are leading preventable causes of cognitive impairment and dementia. We hypothesized that cognitive impairment and anxiety disorders seen in these patients are because of the changes in cerebral microcirculation and pericytes. In this study, we used three different animal models: HFHS diet to mimic prediabetes, Streptozotocin to induce T1DM and spontaneously hypertensive rats (SHRs) for hypertension. We evaluated the cognitive outcomes by various tests: open field test to measure anxiety-like behavior, Y-maze spontaneous alternation test to measure working spatial memory, and novel object recognition test to measure visual recognition memory. We used 3DISCO method to visualize microcirculation in 3D. We used immunofluorescence staining to assess the changes in endothelia and pericytes. We measured accumulation of collagen-1 in vessel walls, as it is the main fibrotic element of fibrosis in other tissues. SHRs and HFHS diet fed animals exhibited less anxiety compared to their control groups. SHRs showed decreased working spatial memory performance. T1DM animal group showed no signs of cognitive decline. HFHS diet caused endothelial proliferation in hippocampus and parietotemporal cortex. However, isolectin positive area in T1DM group showed a significant decline in parietotemporal cortex and no changes at hippocampus. Hypertension group showed no significant changes in the isolectin positive area in parietotemporal cortex, while in the hippocampus there was a decrease in week 23, an increase in week 31 and no changes in week 27. There was a significant increase in HFHS fed group's average collagen-1 pixel intensity values, suggesting microvascular stiffness.