UP-REGULATION OF TYPE-2 IODOTHYRONINE DEIODINASE MESSENGER-RNA IN REACTIVE ASTROCYTES FOLLOWING TRAUMATIC BRAIN INJURY IN THE RAT

Type 2 5'-deiodinase (5'-D2), which converts thyroxine to the more act ive thyroid hormone 3,5,3'-triiodothyronine (T3), is believed to be an important source of intracellular T3 in the brain. The activity of th is enzyme is increased in hypothyroidism and decreased in hyperthyroid ism, and as such, it serves an important role to protect the brain fro m wide fluctuations in T3 during changes in thyroidal state. Although it has been hypothesized that T3 may facilitate neuronal regeneration after CNS injury, the 5'-D2 response to brain injury is unknown. To as sess the 5'-D2 mRNA response to injury, we performed in situ hybridiza tion following traumatic brain injury. In unlesioned animals, 5'-D2 mR NA was undetectable. At 3 days posttrauma, 5'-D2 mRNA was detected in ipsilateral cortex near the contusion. A significant further increase of 5'-D2 mRNA was noted 7 days posttrauma in both hippocampus and cort ex. Similar response was also observed on the contralateral side. Colo calization of 5'-D2 mRNA with glial fibrillary acidic protein indicate s that reactive astrocytes were the major cellular source for the trau ma-induced 5'-D2 expression. These data demonstrate, for the first tim e, a trauma-induced, astrocytic up-regulation of 5'-D2 mRNA, suggestin g a potential role for T3 action in adult brain's response to injury a nd recovery.