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

Abstract

Altered microvascular structure and function may affect mood and cognitive function in hypothyroid patients. We hypothesized that adult hypothyroid (H) rats will have significantly lower forebrain blood vessel densities (BVD) than euthyroid (E) rats, and that treatment with DITPA (D)‐ (a thyroid hormone analogue) or T4(T) will normalize BVD's. Twenty male rats were divided into 4 age‐matched groups. The E group received no thyroidectomy and no treatment. The other three groups received thyroidectomies and pellets. The H group received a placebo pellet, the D group received an 80mg DITPA‐containing pellet, and the T group received a 5.2mg T4 slow release pellet for 6 weeks. Prior to sacrifice, body weights (BW) and body temperatures (BT) were measured. Immunohistochemistry on forebrain regions was performed on 20μm sections using a monoclonal anti‐platelet endothelial cell adhesion molecule to visualize blood vessels. Blood vessels were counted in 20 fields per animal to calculate BVD. The E group averaged BW's of 548 ± 54g, while the H group averaged BW of 332 ± 19g (p‐value < 0.001). Relative to the control group the D‐treated group was significantly lighter (p‐value < 0.00393) while the T‐treated group was comparable in BW to the E group. The same trends were seen with BT with the largest difference between the E and H groups (p‐value = 0.002). BVD in the E group was 147 ± 12 blood vessels per mm2, and in H group 69 ± 5 blood vessels per mm2 (P=0.013), but similar among the E, D, and T groups. These results show that hypothyroidism decreases BVD in adult rat forebrain regions. Moreover, DITPA and T4 are efficacious in reversing the effects of hypothyroidism on BVD.