Thyroxine Treatment after Traumatic Brain Injury Suppresses Astrogliosis and Enhances Neuronal Recovery in Mice

<b><i>Background:</i></b> Traumatic brain injury (TBI) disrupts blood supply, damages neurons and glial cells, and reduces local activation of the prohormone thyroxine (T4) to the active form, triiodothyronine. We treated mice with T4 post-TBI to evaluate the role of thyroid hormone in neural cell protection and injury recovery after TBI, especially the effects on neuroglial cells. <b><i>Materials and Methods:</i></b> A T4 dose was given 1 hour after controlled cortical injury, and in some groups, an additional T4 dose was given 5 days post-TBI. We analyzed the reactive astrocytes and activated microglia in the ipsilateral cortex. We assessed cortical gliogenesis, with or without T4 treatment, in live animals using 5-ethynyl 2'-deoxyuridine-labeling. Finally, learning and spatial memory retention were tested using the Morris water maze (MWM). <b><i>Results:</i></b> T4 treatment 1-hour post-TBI significantly reduced the number of reactive astrocytes and activated microglia in the ipsilateral cortical area. An additional dose of T4 on day 5 post-TBI further reduced the number and size of reactive astrocytes. T4 treatment induced gliogenesis 2.6-fold greater than with saline treatment. T4 treatment induced neuron-glia antigen 2-expressing glial cell proliferation but not astrocytes. Mice treated with T4 post-TBI had improved MWM performance, better escape latency, and better spatial memory compared with saline-treated mice. <b><i>Conclusion:</i></b> Our data indicate that T4 treatment shortly after TBI significantly reduced acute astroglial cell activation and improved recovery of neurons and brain function.