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Mesencephalic astrocyte‐derived neurotrophic factor reduces ischemic brain injury and promotes behavioral recovery in rats
Author(s) -
Airavaara Mikko,
Shen Hui,
Kuo ChiChung,
Peränen Johan,
Saarma Mart,
Hoffer Barry,
Wang Yun
Publication year - 2009
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.22039
Subject(s) - neuroprotection , astrocyte , neurotrophic factors , ischemia , cerebral cortex , biology , tunel assay , cortex (anatomy) , apoptosis , brain derived neurotrophic factor , endocrinology , medicine , pharmacology , anesthesia , neuroscience , central nervous system , biochemistry , receptor
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. J. Comp. Neurol. 515:116–124, 2009. Published 2009 Wiley‐Liss, Inc.