Ruxolitinib exerts neuroprotection via repressing ferroptosis in a mouse model of traumatic brain injury
| Autor: | Chengliang Luo, Xiping Chen, Ya’nan Yan, Cheng Gao, Tao Wang, Luyang Tao, Guang Chen, Tongyu Rui, Yuan Gao, Zhiqi Cheng, Xueshi Chen |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Ruxolitinib Traumatic brain injury Morris water navigation task Pharmacology Neuroprotection Open field Lipid peroxidation 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Developmental Neuroscience Brain Injuries Traumatic Nitriles medicine Animals Ferroptosis Cause of death business.industry Neurodegeneration medicine.disease nervous system diseases Mice Inbred C57BL Disease Models Animal 030104 developmental biology Neuroprotective Agents Pyrimidines Neurology chemistry Pyrazoles business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Experimental neurology. 342 |
| ISSN: | 1090-2430 |
| Popis: | Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Various forms of cells death are involved in the pathological process of TBI, without exception to ferroptosis, which is mainly triggered by iron-dependent lipid peroxidation. Although there have been studies on ferroptosis and TBI, the effect of ruxolitinib (Ruxo), one type of FDA approved drugs for treating myelofibrosis, on the process of ferroptosis post-TBI is remained non-elucidated. Therefore, using a controlled cortical impact device to establish the mouse TBI model, we examined the effect of Ruxo on TBI-induced ferroptosis, in which the inhibitor of ferroptosis, Ferrostatin-1 (Fer-1) was used as a positive control. Moreover, we also respectively explored the effects of these two interventions on neurological deficits caused by TBI. We firstly examined the expression patterns of ferroptosis-related markers at protein level at different time points after TBI. And based on the expression changes of these markers, we chose 12 h post-TBI to prove the effect of Ruxo on ferroptosis. Importantly, we found the intensely inhibitory effect of Ruxo on ferroptosis, which is in parallel with the results obtained after Fer-1-treatment. In addition, these two treatments both alleviated the content of brain water and degree of neurodegeneration in the acute phase of TBI. Finally, we further confirmed the neuroprotective effect of Ruxo or Fer-1 via the wire-grip test, Morris water maze and open field test, respectively. Thereafter, the lesion volume and iron deposition were also measured to certificate their effects on the long-term outcomes of TBI. Our results ultimately demonstrate that inhibiting ferroptosis exerts neuroprotection, and this is another neuroprotective mechanism of Ruxo on TBI. |
| Databáze: | OpenAIRE |
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