Authors: Rushd Al‐Shama, Daphne MP Naessens, Ed van Bavel, Erik NTP Bakker
Published: 2020-12-07
DOI: 10.1002/alz.047252
Source: Full article
AbstractBackgroundHypertension is a major risk factor for dementia. Hypertension is associated with neuroinflammation and neurodegeneration, however, the exact link is unclear. Microglia can undergo senescence, resulting in primed and dystrophic cells that can contribute to the development of Alzheimer’s disease. We hypothesized that microglia are affected by cumulative hypertensive brain injury and reflect an ongoing inflammatory and neurodegenerative pathology.MethodAn in‐depth immunohistochemical analysis of microglia was done on the brains of Spontaneously Hypertensive Rats (SHR) and their genetic controls, Wistar Kyoto rats (WKY); n=5 each. The number of cells and morphological features, such as size, number of branches, and branch length, were measured. We qualitatively assessed microglia for the presence of characteristic dystrophic cells then performed fractal analysis on individual cells to quantitate their morphologies.ResultSHR microglia were more numerous and exhibited signs consistent with senescence and priming, with shorter, fewer branches and the sizes of their cell bodies were larger and more heterogeneous (p<0.05). In SHR, 2.91% of microglia were dystrophic as compared to 0.32% in WKY (p=0.01). Using fractal analysis, we confirmed the presence of dystrophic cells and distinctly characterized them against ramified cells based on 3 main characteristics: complexity, shape, and branching.ConclusionMicroglial senescence, an indicator of neuroinflammation and neurodegenerative pathology, is associated with hypertension. It could thus serve as a therapeutic target and may help identify novel biomarkers. Moreover, fractal analysis is a useful tool to quantify meaningful subtleties.