Abstract
Thyroid hormone (TH) plays a crucial role in neurodevelopment, but its function and specific mechanisms remain unclear after traumatic brain injury (TBI). Here we found that treatment with triiodothyronine (T3) ameliorated the progression of neurological deficits in mice subjected to TBI. The data showed that T3 reduced neural death and promoted the elimination of damaged mitochondria via mitophagy. However, T3 did not prevent TBI-induced cell death in phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (Pink1) knockout mice suggesting the involvement of mitophagy. Moreover, we also found that T3 promoted neurogenesis via crosstalk between mature neurons and neural stem cells (NSCs) after TBI. In neuron cultures undergoing oxygen and glucose deprivation (OGD), conditioned neuron culture medium collected after T3 treatment enhanced the in vitro differentiation of NSCs into mature neurons, a process in which mitophagy was required. Taken together, these data suggested that T3 treatment could provide a therapeutic approach for TBI by preventing neuronal death via mitophagy and promoting neurogenesis via neuron–NSC crosstalk.
Highlights
Traumatic brain injury (TBI) is considered to be a leading cause of substantial mortality and long-term disability among young adults worldwide[1]
T3 treatment rescued behavioral deficits after TBI To evaluate the effect of T3 on outcome after TBI, we examined lesion volume and brain edema
The brain water content was significantly decreased in the TBI group treated with T3 versus those treated by vehicle (Fig. 1c), suggesting that T3 had the effect of ameliorating brain edema induced by TBI
Summary
Traumatic brain injury (TBI) is considered to be a leading cause of substantial mortality and long-term disability among young adults worldwide[1]. In the United States, TBI contributes to >30% of the deaths resulting from traumatic injury each year, with ~1.4 million cases requiring emergency treatment and 235,000 being hospitalized[2,3]. An estimated 85,000 TBI survivors per year suffer from long-term complications, including cognitive disorders, chronic disability, and persistent vegetative states[2,4]. The economic burden is serious; about $37.8 billion is spent annually on treatments, long-term care, work absences, and premature deaths[2,5]. Accumulating evidence from clinical and experimental studies has indicated that TH treatment showed neuroprotective properties after acute brain injury, including stroke and TBI9–11. 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
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