Premium
Reduced estrogen uptake and increased brain damage in female diabetic db/db mice even after hyperglycemic normalization
Author(s) -
Zhang Liqun,
Brucklacher Robert,
Vannucci Susan
Publication year - 2007
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.21.6.a1276-b
Subject(s) - medicine , endocrinology , neuroprotection , ovariectomized rat , brain damage , metformin , estrogen , diabetes mellitus , ischemia , brain infarction
Diabetes increases brain damage following stroke. Estrogen (E) is usually neuroprotective but we have shown that E replacement does not reduce ischemic brain damage in diabetic mice. Here we investigate the effect of hyperglycemia on E’s effect on db/db mice, and if E uptake into brain could explain the lack of efficacy in these animals. Db/db , and non‐diabetic +/? , female mice were ovariectomized (OVX) at 5 wks; treated with E for 12 days (5ug/day, i.p.). Unilateral cerebral hypoxia‐ischemia (H/I) was induced in intact, OVX and OVX plus E mice at 8 wks. Another cohort of mice was given metformin at 4 wk of age. Infarct volumes were evaluated at 48 hr recovery. Brain E uptake was measured in mice from each group without H/I at 8 wks. Metformin treatment normalized blood glucose levels in all diabetic groups and decreased infarction in intact and OVX db/db groups, although still greater than non‐diabetic +/? groups. E treatment failed to reduce brain damage in OVX db/db mice with euglycemia, consistent with our previous hyperglycemic study. Db/db mice had significantly lower brain E uptake, independent of blood glucose levels. Reduced brain E uptake may contribute to the lack of neuroprotective effect of E in female db/db mice. Thus, E may not benefit postmenopausal female type II diabetics. Diabetic hyperglycemia is not the only cause of severe ischemic brain damage in female type II diabetics and additional vascular factors may be involved.