Mesencephalic astrocyte-derived neurotrophic factor reduces ischemic brain injury and promotes behavioral recovery in rats.
Mesencephalic astrocyte-derived neurotrophic factor (MANF), also known as arginine-rich, mutated in early stage of tumors (ARMET), is a secreted protein that reduces endoplasmic reticulum (ER) stress. Previous studies have shown that MANF mRNA expression and protein levels are increased in the cerebral cortex after brain ischemia, a condition that induces ER stress. The function of MANF during brain ischemia is still not known. The purpose of this study was to examine the protective effect of MANF after ischemic brain injury. Recombinant human MANF was administrated locally to the cerebral cortex before a 60-min middle cerebral artery occlusion (MCAo) in adult rats. Triphenyltetrazolium chloride (TTC) staining indicated that pretreatment with MANF significantly reduced the volume of infarction at 2 days after MCAo. MANF also attenuated TUNEL labeling, a marker of cell necrosis/apoptosis, in the ischemic cortex. Animals receiving MANF pretreatment demonstrated a decrease in body asymmetry and neurological score as well as an increase in locomotor activity after MCAo. Taken together, these data suggest that MANF has neuroprotective effects against cerebral ischemia, possibly through the inhibition of cell necrosis/apoptosis in cerebral cortex.
Airavaara
Mikko
M
National Institute on Drug Abuse, I.R.P., Baltimore, Maryland 21224, USA.
Shen
Hui
H
Kuo
Chi-Chung
CC
Peränen
Johan
J
Saarma
Mart
M
Hoffer
Barry
B
Wang
Yun
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020520:Brain Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007202:Indicators and Reagents; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009336:Necrosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013194:Staining and Labeling; D013778:Tetrazolium Salts; D016896:Treatment Outcome
D007202:Indicators and Reagents; C099695:MANF protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium