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Brain Res. 2015 Jul 30;1615:89-97. doi: 10.1016/j.brainres.2015.04.033. Epub 2015 Apr 29.

Intraperitoneal administration of thioredoxin decreases brain damage from ischemic stroke.

Author information

1
Department of Neurosurgery, Xi Jing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi׳an 710032, China; Department of Clinical Medicine, School of Aerospace Medicine, The Fourth Military Medical University, 127 Changle West Road, Xi׳an 710032, China.
2
Department of Neurosurgery, Xi Jing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi׳an 710032, China.
3
Department of Neurosurgery, Xi Jing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi׳an 710032, China. Electronic address: yanqu0123@gmail.com.

Abstract

Recent studies demonstrate that Thioredixin (Trx) possesses a neuronal protective effect and closely relates to oxidative stress and apoptosis of cerebral ischemia injury. The present study was conducted to validate the neuroprotective effect of recombinant human Trx-1 (rhTrx-1) and its potential mechanisms against ischemia injury at middle cerebral artery occlusion (MCAO) in mice. rhTrx-1 was administrated intraperitoneally at a dose of 5, 10 and 20mg/kg 30 min before MCAO in mice, and its neuronal protective effect was evaluated by neurological deficit score, brain dry-wet weight, 2,3,5-triphenyltetrazolium chloride (TTC) staining. The protein carbonyl content and HO-1 were detected to investigate its potential anti-oxidative and anti-inflammatory property, and the anti-apoptotic ability of rhTrx-1 was assessed by casepase-3 and TUNEL staining. The results demonstrated that rhTrx-1 significantly improved neurological functions and reduced cerebral infarction and apoptotic cell death at 24h after MCAO. Moreover, rhTrx-1 resulted in a significant decrease in carbonyl contents and HO-1 against oxidative stress, which turned to be fast reduction during the first 24h and tended to be stable from 24h to 72h after MCAO. The study shows that rhTrx-1 exerts an neuroprotective effect in cerebral ischemia injury. The anti-oxidative, anti-apoptotic and anti-inflammatory properties of rhTrx-1 are more likely to succeed as a therapeutic approach to diminish oxidative stress-induced neuronal apoptotic cell death in acute ischemic stroke.

KEYWORDS:

Apoptosis; Middle cerebral artery occlusion (MCAO); Oxidative stress; Thioredoxin

PMID:
25935696
DOI:
10.1016/j.brainres.2015.04.033
[Indexed for MEDLINE]

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