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.

Nyckelord

Animals

Animals

Newborn

Apoptosis

drug effects

physiology

Caspase 3

drug effects

metabolism

Cells

Cultured

Cytoprotection

drug effects

physiology

Drug Administration Schedule

Glutamic Acid

toxicity

Hypoxia-Ischemia

Brain

drug therapy

metabolism

physiopathology

Insulin-Like Growth Factor I

pharmacology

Myelin Basic Proteins

metabolism

Nerve Degeneration

drug therapy

physiopathology

prevention & control

Nerve Fibers

Myelinated

drug effects

metabolism

Nerve Growth Factors

pharmacology

Neurotoxins

toxicity

Oligodendroglia

drug effects

metabolism

Rats

Rats

Sprague-Dawley

Rats

Wistar

Stem Cells

drug effects

metabolism

Time Factors

Treatment Outcome

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)