ReferenceID 497

Exogenous T3 administration provides neuroprotection in a murine model of traumatic brain injury

Pharmacol Res

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 exacerba

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Reference Id
497
Evidence Id
17087
Core Evidence Id
17087
Source Reference Id
965
Herb2 Reference Id
HBREF001675
Subject Paper Key
HBIN007532_23313345
Pubmed Id
23313345
Doi
10.1016/j.phrs.2012.12.009
Paper Title
Exogenous T3 administration provides neuroprotection in a murine model of traumatic brain injury
Paper 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.
Journal
Pharmacol Res
Publish Year
2013
Experiment Subject
mouse
Experiment Type
Animal Experiment
Phenotype Related
Traumatic Brain Injury
Paper Title Cn
Paper Title En
Exogenous T3 administration provides neuroprotection in a murine model of traumatic brain injury
Bilingual Status
semi_complete