A synthetic NCAM-derived peptide, FGL, protects hippocampal neurons from ischemic insult both in vitro and in vivo.
There is a major unmet need for development of innovative strategies for neuroprotection against ischemic brain injury. Here we show that FGL, a neural cell adhesion molecule (NCAM)-derived peptide binding to and inducing phosphorylation of the fibroblast growth factor receptor (FGFR), acts neuroprotectively after an ischemic insult both in vitro and in vivo. The neuroprotective activity of FGL was tested in vitro on dissociated rat hippocampal neurons and hippocampal slice cultures, using a protocol of oxygen-glucose deprivation (OGD). FGL protected hippocampal neurons from damage and maintained or restored their metabolic and presynaptic activity, both if employed as a pretreatment alone to OGD, and if only applied after the insult. In vivo 24 h pretreatment with a single suboccipital injection of FGL significantly protected hippocampal CA1 neurons from death in a transient global ischemia model in the gerbil. We conclude that FGL promotes neuronal survival after ischemic brain injury.
Skibo
Galina G
GG
Protein Laboratory, Institute of Molecular Pathology, Panum Institute, University of Copenhagen, Blegdamsvej 3C, bld. 6.2, DK-2200 Copenhagen N, Denmark.
Lushnikova
Iryna V
IV
Voronin
Kyrill Y
KY
Dmitrieva
Oksana
O
Novikova
Tatiana
T
Klementiev
Boris
B
Vaudano
Elisabetta
E
Berezin
Vladimir A
VA
Bock
Elisabeth
E
D000818:Animals; D000831:Animals, Newborn; D002545:Brain Ischemia / Q000517:prevention & control*; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D004347:Drug Interactions; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000166:cytology*; D000860:Hypoxia; D019006:Neural Cell Adhesion Molecules / Q000008:administration & dosage* / Q000138:chemical synthesis; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000138:chemical synthesis; D009924:Organ Culture Techniques; D010766:Phosphorylation / Q000187:drug effects; D011419:Propidium; D011726:Pyridinium Compounds / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D013569:Synapses / Q000473:pathology; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D013997:Time Factors
C073804:FM1 43; C488618:NCAM protein (681-695), human; D019006:Neural Cell Adhesion Molecules; D018696:Neuroprotective Agents; D011726:Pyridinium Compounds; D011758:Pyrroles; D000644:Quaternary Ammonium Compounds; D017468:Receptors, Fibroblast Growth Factor; C105686:SU 5402; D013778:Tetrazolium Salts; D013844:Thiazoles; C070380:3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; D011419:Propidium; D005947:Glucose