Effects of thyroidectomy, T4, and DITPA replacement on brain blood vessel density in adult rats

Abstract

In hypothyroid patients, altered microvascular structure and function may affect mood and cognitive function. We hypothesized that adult male hypothyroid rats will have significantly lower forebrain blood vessel densities (BVD) than euthyroid rats and that treatment with 3,5-diiothyroprionic acid (DITPA) (a thyroid hormone analog) or thyroxine (T(4)) will normalize BVDs. The euthyroid group received no thyroidectomy or treatment. The other three groups received thyroidectomies and pellets. The hypothyroid group received a placebo pellet, the DITPA group received an 80-mg DITPA-containing pellet, and the T(4) group received a 5.2-mg T(4) slow-release pellet for 6 wk. Body weights, cardiac function, and body temperatures were measured. A monoclonal antiplatelet endothelial cell adhesion antibody was used to visualize blood vessels. The euthyroid group averaged body weights of 548 +/- 54 g, while the hypothyroid group averaged a body weight of 332 +/- 19 g (P value < 0.001). Relative to the euthyroid group, the DITPA-treated group was significantly lighter (P value < 0.05), while the T(4)-treated group was comparable in body weight to the euthyroid group. The same trends were seen with body temperature and cardiac function with the largest difference between the euthyroid and hypothyroid groups. BVD in the euthyroid group was 147 +/- 12 blood vessels/mm(2) and in hypothyroid group 69 +/- 5 blood vessels/mm(2) (P = 0.013) but similar among the euthyroid, DITPA, and T(4) groups. These results show that hypothyroidism decreased BVD in adult rat forebrain regions. Moreover, DITPA and T(4) were efficacious in preventing effects of hypothyroidism on cardiac function and BVD.