MRI Dynamically Evaluates the Therapeutic Effect of Recombinant Human MANF on Ischemia/Reperfusion Injury in Rats.
As an endoplasmic reticulum (ER) stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) has been proven to protect dopaminergic neurons and nondopaminergic cells. Our previous studies had shown that MANF protected against ischemia/reperfusion injury. Here, we developed a magnetic resonance imaging (MRI) technology to dynamically evaluate the therapeutic effects of MANF on ischemia/reperfusion injury. We established a rat focal ischemic model by using middle cerebral artery occlusion (MCAO). MRI was performed to investigate the dynamics of lesion formation. MANF protein was injected into the right lateral ventricle at 3 h after reperfusion following MCAO for 90 min, when the obvious lesion firstly appeared according to MRI investigation. T2-weighted imaging for evaluating the therapeutic effects of MANF protein was performed in ischemia/reperfusion injury rats on Days 1, 2, 3, 5, and 7 post-reperfusion combined with histology methods. The results indicated that the administration of MANF protein at the early stage after ischemia/reperfusion injury decreased the mortality, improved the neurological function, reduced the cerebral infarct volume, and alleviated the brain tissue injury. The findings collected from MRI are consistent with the morphological and pathological changes, which suggest that MRI is a useful technology for evaluating the therapeutic effects of drugs.
The First Affiliated Hospital, Anhui Medical University, 218 Jixi Road, Hefei 230032, China. xyunwang1991@163.com.
Xian-Yun
XY
Wang
School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, China. songmengmeng@ahmu.edu.cn.|Biopharmaceutical Institute, Anhui Medical University, 81 Meishan Road, Hefei 230032, China. songmengmeng@ahmu.edu.cn.
Meng-Meng
MM
Song
The First Affiliated Hospital, Anhui Medical University, 218 Jixi Road, Hefei 230032, China. aysx2015@163.com.
Si-Xing
SX
Bi
School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, China. jojo125520@163.com.|Biopharmaceutical Institute, Anhui Medical University, 81 Meishan Road, Hefei 230032, China. jojo125520@163.com.
Yu-Jun
YJ
Shen
School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, China. shenyx@ahmu.edu.cn.|Biopharmaceutical Institute, Anhui Medical University, 81 Meishan Road, Hefei 230032, China. shenyx@ahmu.edu.cn.
Yu-Xian
YX
Shen
The First Affiliated Hospital, Anhui Medical University, 218 Jixi Road, Hefei 230032, China. cjr.yuyongqiang@vip.163.com.
Yong-Qiang
YQ
Yu
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D015427:Reperfusion Injury / Q000000981:diagnostic imaging / Q000188:drug therapy*
C099695:MANF protein, human; D009414:Nerve Growth Factors; D011994:Recombinant Proteins
MANF; MRI; cerebral ischemia/reperfusion injury