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

Ya Ni Huang, Ling Yu Yang, Nigel H. Greig, Yu Chio Wang, Chien Cheng Lai, Jia Yi Wang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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)-α 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-α improved motor deficit following TBI. PFT-α suppressed TBI-induced striatal glial activation and expression of proinflammatory cytokines. PFT-α 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-α. Post-injury PFT-α treatment reduced the number of degenerating (FJC-positive) and apoptotic neurons. Our results suggest that PFT-α 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.

Original languageEnglish
Article number2368
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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Autophagy
Neuroprotective Agents
Oxidative Stress
Apoptosis
Corpus Striatum
Neuroglia
Traumatic Brain Injury
pifithrin
Neurons
Wounds and Injuries
Microtubules
Sprague Dawley Rats
Transcription Factors
Cytokines
Light
Messenger RNA

ASJC Scopus subject areas

  • General

Cite this

Neuroprotective effects of pifithrin-α against traumatic brain injury in the striatum through suppression of neuroinflammation, oxidative stress, autophagy, and apoptosis. / Huang, Ya Ni; Yang, Ling Yu; Greig, Nigel H.; Wang, Yu Chio; Lai, Chien Cheng; Wang, Jia Yi.

In: Scientific Reports, Vol. 8, No. 1, 2368, 01.12.2018.

Research output: Contribution to journalArticle

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