Neuroprotective effect of thyroid hormones in cerebral hypoperfusion

Clinical studies demonstrate that a decrease in the blood concentration of thyroid hormones within the euthyroid range is associated with higher mortality rates, damage, severity and poor prognosis for lost function recovery in patients who survived a stroke during one year. Experimental studies prove the neuroprotective role of thyroid hormones in animal models of cerebral hypoperfusion: bilateral ligation of carotid arteries and occlusion of the middle cerebral artery. Thyroid hormones can penetrate through the blood-brain barrier. Their nuclear effects in the nervous tissue are mediated by the TRα and TRβ receptors. Thyroid hormones provide astrocytic differentiation, reduce proliferation and astrogliosis, increase the glutamate uptake by astrocytes, reduce excitotoxicity and stimulate ATP synthesis, suppress aquaporin-4 (AQP4) expression, and reduce cerebral edema risk. They also reduce tonic GABA signaling in the peri-infarction area, increase the synthesis of BDNF and GDNF neurotrophic factors. Moreover, they have an anti-apoptotic effect. Due to TRα1 receptors on neuronal stem cells of the subgranular hippocampus zone and subventricular zone, thyroid hormones shift the balance between neurogenesis and oligodendrogenesis towards neurogenesis both in intact animals and in those with cerebral hypoperfusion. The non-genomic actions of thyroid hormones are initiated at receptors in the plasma membrane, in the cytoplasm, or in mitochondria, resulting in endothelial cell migration and angiogenesis. Thus, within the normal reaction range the structural and functional state of the thyroid gland is associated with neuroplasticity. So, the level of thyroid hormones can predict the severity of a disease accompanied by cerebral hypoperfusion. Thyroid hormones can also be considered as prototypes of neuroprotective drugs.