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

Evelyn Heymann Schlenker,1 Megan Hora,1 Yingheng Liu,2 Rebecca A. Redetzke,2 Eugene Morkin,3 and A. Martin Gerdes2

Schlenker EH, Hora M, Liu Y, Redetzke RA, Morkin E, Gerdes AM. Effects of thyroidectomy, T4, and DITPA replacement
on brain blood vessel density in adult rats. Am J Physiol Regul Integr Comp Physiol 294: R1504–R1509, 2008. First published March 19, 2008; doi:10.1152/ajpregu.00027.2008.—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 (T4) 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 T4 group received a 5.2-mg T4 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 19g (P value 0.001). Relative to the euthyroid group, the DITPA-treated group was significantly lighter (P value 0.05), while the T4-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/mm2 and in hypothyroid group 69 5 blood vessels/mm2 (P 0.013) but similar among the euthyroid, DITPA, and T4 groups. These results show that hypothyroidism decreased BVD in adult rat forebrain regions. Moreover, DITPA and T4 were efficacious in preventing effects of hypothyroidism on cardiac function and BVD.