Neuroprotective effects of pifithrin-alpha against traumatic brain injury in the striatum through suppression of neuroinflammation, oxidative stress, autophagy, and apoptosis

作者：Huang Ya Ni; Yang Ling Yu; Greig Nigel H; Wang Yu Chio; Lai Chien Cheng; Wang Jia Yi^*

来源：Scientific Reports, 2018, 8(1): 2368.

DOI：10.1038/s41598-018-19654-x

Cortical and hippocampal neuronal damages caused by traumatic brain injury (TBI) are associated with motor and cognitive impairments; however, only little attention paid to the striatal damage. It is known that the p53 tumor-suppressor transcription factor participated in TBI-induced secondary brain damage. We investigated how the p53 inactivator pifithrin (PFT)-alpha affected TBI-induced striatal neuronal damage at 24 h post-injury. Sprague-Dawley rats subjected to a controlled cortical impact were used as TBI models. We observed that p53 mRNA significantly increased, whereas p53 protein expression was distributed predominantly in neurons but not in glia cells in striatum after TBI. PFT-alpha improved motor deficit following TBI. PFT-alpha suppressed TBI-induced striatal glial activation and expression of proinflammatory cytokines. PFT-alpha alleviated TBI-induced oxidative damage TBI induced autophagy was evidenced by increased protein expression of Beclin-1 and shift of microtubule-associated light chain (LC) 3-I to LC3-II, and decreased p62. These effects were reduced by PFT-alpha. Post-injury PFT-alpha treatment reduced the number of degenerating (FJC-positive) and apoptotic neurons. Our results suggest that PFT-alpha may provide neuroprotective effects via p53-dependent or -independent mechanisms depending on the cell type and timing after the TBI and can possibly be developed into a novel therapy to ameliorate TBI-induced neuronal damage.

• 出版日期2018-2-5
• 单位NIH; 河北医科大学