Thyroid hormone and the brain: Mechanisms of action in development and role in protection and promotion of recovery after brain injury

Abstract

Thyroid hormone (TH) is essential for normal brain development and may also promote recovery and neuronal regeneration after brain injury. TH acts predominantly through the nuclear receptors, TH receptor alpha (THRA) and beta (THRB). Additional factors that impact TH action in the brain include metabolism, activation of thyroxine (T4) to triiodothyronine (T3) by the enzyme 5'-deiodinase Type 2 (Dio2), inactivation by the enzyme 5-deiodinase Type 3 (Dio3) to reverse T3 (rT3), which occurs in glial cells, and uptake by the Mct8 transporter in neurons. Traumatic brain injury (TBI) is associated with inflammation, metabolic alterations and neural death. In clinical studies, central hypothyroidism, due to hypothalamic and pituitary dysfunction, has been found in some individuals after brain injury. TH has been shown, in animal models, to be protective for the damage incurred from brain injury and may have a role to limit injury and promote recovery. Although clinical trials have not yet been reported, findings from in vitro and in vivo models inform potential treatment strategies utilizing TH for protection and promotion of recovery after brain injury.

Polarized Expression of Ion Channels and Solute Carrier Family Transporters on Heterogeneous Cultured Human Corneal Endothelial Cells

“…Although the function of MCT8 as a transporter of thyroid hormones is well known in other cells, the exact function of MCT8 in the physiological pHi homeostasis of cHCECs has yet to be elucidated. 50 …”

TDP-43 proteinopathy in aging: Associations with risk-associated gene variants and with brain parenchymal thyroid hormone levels

“…Thyroid derived hormones are iodinated signalling molecules that subserve evolutionarily ancient biologic functions (Crockford, 2009;Holzer et al, 2017;Taylor and Heyland, 2017), and TH plays roles in vertebrate neurodevelopment and brain disease (Bernal, 2005;Liu and Brent, 2018). Lack of TH in utero and in early life causes severe cognitive impairment, with extensive white matter pathology (Rosman, 1972).…”

Dual effects of thyroid hormone on neurons and neurogenesis in traumatic brain injury

“…TBI is well known to cause changes in systemic TH levels 8 . Accumulating evidence from clinical and experimental studies has indicated that TH treatment showed neuroprotective properties after acute brain injury, including stroke and TBI [9][10][11] . Understanding TH's actions and the mechanisms regulating TH functions in the adult brain is essential to design potential therapeutic strategies for TBI, due to dysregulated TH signaling during this procession.…”