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Chronic Hypertension Increases Pial Perivascular Microglia in Female Dahl‐S Rats
Author(s) -
Warrington Junie Paula,
Shao Qingmei,
Clayton Ahsia M.,
Maeda Kenji J.,
Garrett Michael R.,
Sasser Jennifer M.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02304
Subject(s) - microglia , medicine , dapi , pregnancy , endocrinology , pathology , staining , inflammation , biology , genetics
Recent studies have shown that hypertension increases the proliferation and migration of microglia towards the perivascular space before destruction of the vasculature. Other studies have shown that hypertension increases perivascular macrophages, shown to contribute to impaired neurovascular coupling and cognitive impairments in mice. Despite these studies, there has been no description of what happens to perivascular microglia (PVMG) at the pia in the setting of chronic hypertension or following pregnancy. The goal of this study was to test the hypothesis that chronic hypertension increases the density of PVMGs and that complicated pregnancy history will exacerbate this increase. Female (8 months old) Sprague Dawley and Dahl‐S virgin or prior pregnant (2 pregnancies) rats were used. Brains were collected 3.5 months after the second pregnancy and processed for immunofluorescence staining for ion calcium binding adapter molecule (Iba‐1, a microglia marker) and DAPI. Z‐stacks were captured (0.5μm steps) throughout the thickness of the slice (20μm) using confocal microscopy. The number of microglia surrounding the pial artery (posterior communicating artery) was counted and normalized to the circumference of the vessel (density). We also measured the distance between each microglia surrounding the vessel. There was no effect of pregnancy on PVMG density (p=0.675) or mean distance between PVMG (p=0.161) but a significant effect of hypertension (p<0.001) on both measures. PVMG density increased from 0.017±0.005 to 0.031±0.004/μm in the virgins and from 0.020±0.002 to 0.032±0.002/μm in the prior pregnant rats. Mean distance between PVMGs decreased from 64±13 to 28±5μm in the virgins and from 52±7 to 21±2 μm in the prior pregnant rats. Some of the PVMGs were antigen presenting cells (co‐expressed major histocompatibility complex II, MHCII). Our results indicate that at the pia, PVMGs accumulate around the blood vessels, with some presenting antigens to lymphocytes. The exact function of these cells are not known, but we hypothesize that PVMGs could be contributing to the pathophysiology of hypertension or could present a compensatory mechanism to protect the blood vessels. Future studies will directly test the function of pial PVMGs in the context of acute and chronic hypertension and will assess whether this finding is specific to female brains. Support or Funding Information UMMC Department of Neurology

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