title: Exogenous T3 administration provides neuroprotection in a murine model of traumatic brain injury.
abstract: Traumatic brain injury (TBI) induces primary and secondary damage in both the endothelium and the brain parenchyma. While neurons die quickly by necrosis, a vicious cycle of secondary injury in endothelial cells exacerbates the initial injury. Thyroid hormones are reported to be decreased in patients with brain injury. Controlled cortical impact injury (CCI) is a widely used, clinically relevant model of TBI. Here, using CCI in adult male mice, we set to determine whether 3,5,3'-triiodothyronine (T3) attenuates posttraumatic neurodegeneration and neuroinflammation in an experimental model of TBI. Treatment with T3 (1.2μg/100g body weight, i.p.) 1h after TBI resulted in a significant improvement in motor and cognitive recovery after CCI, as well as in marked reduction of lesion volumes. Mouse model for brain injury showed reactive astrocytes with increased glial fibrillary acidic protein, and formation of inducible nitric oxide synthase (iNOS). Western blot analysis revealed the ability of T3 to reduce brain trauma through modulation of cytoplasmic-nuclear shuttling of nuclear factor-κB (NF-κB). Twenty-four hours after brain trauma, T3-treated mice also showed significantly lower number of TUNEL(+) apoptotic neurons and curtailed induction of Bax, compared to vehicle control. In addition, T3 significantly enhanced the post-TBI expression of the neuroprotective neurotrophins (BDNF and GDNF) compared to vehicle. Our data provide an additional mechanism for the anti-inflammatory effects of thyroid hormone with critical implications in immunopathology at the cross-roads of the immune-endocrine circuits.
authors: Department of Biological and Environmental Sciences, University of Messina, Italy.
authors: Rosalia
authors: R
authors: Crupi
authors: Irene
authors: I
authors: Paterniti
authors: Michela
authors: M
authors: Campolo
authors: Rosanna
authors: R
authors: Di Paola
authors: Salvatore
authors: S
authors: Cuzzocrea
authors: Emanuela
authors: E
authors: Esposito
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D016328:NF-kappa B / Q000096:biosynthesis; D009414:Nerve Growth Factors / Q000096:biosynthesis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D045442:Rotarod Performance Test; D014284:Triiodothyronine / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D016328:NF-kappa B; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D014284:Triiodothyronine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse