Marked age-dependent neuroprotection by brain-derived neurotrophic factor against neonatal hypoxic-ischemic brain injury.
Hypoxic-ischemic brain injury in survivors of perinatal asphyxia is a frequently encountered clinical problem for which there is currently no effective therapy. Neurotrophins, such as brain-derived neurotrophic factor (BDNF), can protect responsive neurons against cell death in some injury paradigms. While the role of BDNF in hypoxic-ischemic brain injury is not clear, evidence suggests that BDNF may have different effects in the developing, as opposed to the adult, brain. We found that a single intracerebroventricular (ICV) injection of BDNF resulted in rapid and robust phosphorylation of trk receptors in multiple brain regions in the postnatal day (PD) 7 rat brain. BDNF also markedly protected against hypoxic-ischemic brain injury at PD7. It protected against 90% of tissue loss due to hypoxic-ischemia when given just prior to the insult and against 50% of tissue loss when give after the insult. In contrast, ICV injection of BDNF in PD21 and adult rats resulted in little trk phosphorylation and less dramatic protection against unilateral hypoxic-ischemic injury at PD21. Because of its potent neuroprotective actions in the developing brain, BDNF may be a potential treatment for asphyxia and other forms of acute injury in the perinatal period.
Cheng
Y
Y
Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.
Gidday
J M
JM
Yan
Q
Q
Shah
A R
AR
Holtzman
D M
DM
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002545:Brain Ischemia / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D002534:Hypoxia, Brain / Q000503:physiopathology*; D007231:Infant, Newborn; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D020794:Receptor Protein-Tyrosine Kinases