Delayed IGF-1 administration rescues oligodendrocyte progenitors from glutamate-induced cell death and hypoxic-ischemic brain damage.
We previously demonstrated that IGF-1 blocks glutamate-mediated death of late oligodendrocyte progenitors (OPs) by preventing Bax translocation, mitochondrial cytochrome c release and cleavage of caspases 9 and 3. Here, we demonstrate that IGF-1 prevents caspase 3 activation in late OPs when administered up to 16 h following exposure to glutamate. Moreover, late addition of IGF-1 to OPs previously exposed to toxic levels of glutamate promotes oligodendrocyte maturation as measured by myelin basic protein expression. We also demonstrate that intraventricularly administered IGF-1 retains OPs in the perinatal white matter after hypoxia-ischemia when given after insult. These results suggest that delayed administration of IGF-1 will rescue OPs in the immature white matter and promote myelination following hypoxia-ischemia.
Wood
Teresa L
TL
Department of Neurology and Neuroscience, New Jersey Medical School, University of Medicine and Dentistry New Jersey, Newark, NJ 07103, USA. woodte@umdnj.edu <woodte@umdnj.edu>
Loladze
Vaho
V
Altieri
Stefanie
S
Gangoli
Nitish
N
Levison
Steven W
SW
Brywe
Katarina G
KG
Mallard
Carina
C
Hagberg
Henrik
H
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D018698:Glutamic Acid / Q000633:toxicity; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D004676:Myelin Basic Protein / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
D004676:Myelin Basic Protein; D009414:Nerve Growth Factors; D009498:Neurotoxins; D018698:Glutamic Acid; D007334:Insulin-Like Growth Factor I; D053148:Caspase 3