Epidermal growth factor-induced cell proliferation in the adult rat striatum.
Current strategies for repairing the adult CNS following injury include cell transplantation and/or the use of viral vectors to deliver therapeutic agents. Although promising, both techniques are limited in their usefulness due to the immunological response triggered in the brain as a result of the introduction of foreign antigens. An alternative method to repair the damaged CNS is to stimulate endogenous cells within the brain to divide thereby replacing cells lost to injury. Since it has been shown that growth factors such as epidermal growth factor (EGF) are potent mitogens to CNS cells in vitro, we sought to assess the mitogenic effect of an in vivo application of EGF to the adult mammalian brain. Accordingly, varying doses of human recombinant EGF were administered to the striatum of adult rats, followed 48 h later by intraperitoneal injections of 5-bromodeoxyuridine (BrdU), a marker for cell proliferation. Of four doses assessed, 0.05 ng of EGF induced the highest levels of cell proliferation. To determine the cellular identity of these proliferating cells, animals were injected with (3)H-thymidine 48 h following EGF administration to label dividing cells. Sections were subsequently immunostained for markers to astrocytes, microglia, oligodendrocytes, neural precursors, and mature neurons. Compared to controls, a significant proportion of the newly generated cells resulting from EGF administration were identified as immature and mature astrocytes. Collectively, these results provide valuable information for utilizing a growth factor administration approach to mobilize the proliferative response of endogenous cells to replace those lost to injury or disease.
McGinn
Melissa J
MJ
Department of Anatomy and Neurobiology, Medical College of Virginia, Virginia Commonwealth University, PO Box 980709, Richmond, VA 23298-0709, USA.
Sun
Dong
D
Schneider
Stacie L
SL
Alexander
John K
JK
Colello
Raymond J
RJ
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002455:Cell Division / Q000187:drug effects; D003342:Corpus Striatum / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D053331:Ectodysplasins; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling / Q000379:methods; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium / Q000493:pharmacokinetics; D014746:Vimentin / Q000378:metabolism
C506018:EDA protein, human; D053331:Ectodysplasins; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D014746:Vimentin; D014316:Tritium; D004815:Epidermal Growth Factor; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine; D013936:Thymidine