Region-specific proliferative response of neural progenitors to exogenous stimulation by growth factors following ischemia.
The most effective way to augment neural progenitor proliferation after ischemia is still unknown. We administered various agents into the rat cerebral ventricle after transient global ischemia and compared the neural progenitor response in the anterior subventricular zone (aSVZ), dentate gyrus subgranular zone, posterior periventricle, and hypothalamus. We demonstrated that cocktail administration of epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) remarkably increased the numbers of neural progenitors in all four regions examined. The addition of Notch ligand DLL4 to the cocktail elicited the largest progenitor response in the aSVZ and hypothalamus. Our results suggest that EGF and FGF-2, combined with DLL4, represent the universally applicable regimen for the expansion of the neural progenitor pool following ischemia.
Oya
Soichi
S
Department of Neurosurgery, Graduate School of Medicine, the University of Tokyo, Japan.
Yoshikawa
Gakushi
G
Takai
Keisuke
K
Tanaka
Jun-Ichi
J
Higashiyama
Shigeki
S
Saito
Nobuhito
N
Kirino
Takaaki
T
Kawahara
Nobutaka
N
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002552:Cerebral Ventricles / Q000187:drug effects / Q000473:pathology; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004921:Erythropoietin / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*
D019208:Brain-Derived Neurotrophic Factor; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C064045:delta protein; D016222:Fibroblast Growth Factor 2; D004921:Erythropoietin; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I