Intraperitoneal administration of thioredoxin decreases brain damage from ischemic stroke.
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.
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.
Bin
B
Wang
Department of Neurosurgery, Xi Jing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi׳an 710032, China.
Shilai
S
Tian
Department of Neurosurgery, Xi Jing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi׳an 710032, China.
Jiayi
J
Wang
Department of Neurosurgery, Xi Jing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi׳an 710032, China.
Feng
F
Han
Department of Neurosurgery, Xi Jing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi׳an 710032, China.
Lei
L
Zhao
Department of Neurosurgery, Xi Jing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi׳an 710032, China.
Rencong
R
Wang
Department of Neurosurgery, Xi Jing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi׳an 710032, China.
Weidong
W
Ning
Department of Neurosurgery, Xi Jing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi׳an 710032, China.
Wei
W
Chen
Department of Neurosurgery, Xi Jing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi׳an 710032, China. Electronic address: yanqu0123@gmail.com.
Yan
Y
Qu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000517:prevention & control; D053148:Caspase 3 / Q000378:metabolism; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007274:Injections, Intraperitoneal; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage*; D015427:Reperfusion Injury / Q000150:complications; D020521:Stroke / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013879:Thioredoxins / Q000008:administration & dosage*
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D013879:Thioredoxins; D053148:Caspase 3
Apoptosis; Middle cerebral artery occlusion (MCAO); Oxidative stress; Thioredoxin