Delayed IGF-1 treatment reduced long-term hypoxia-ischemia-induced brain damage and improved behavior recovery of immature rats.
Cerebral hypoxia-ischemia during the perinatal period is the single most important cause of acute newborn mortality and chronic disability. Despite our increasing understanding of the mechanisms of neuronal injury, an effective clinical therapy has yet to be established to mitigate brain damage and improve the prognosis and well-being of these newborn patients. Insulin-like growth factor 1 (IGF-1) is a well-known neurotrophic factor, essential for the survival and functional maturation of immature neurons. This study demonstrated that subcutaneous administration of IGF-1 at 24 and 48 hours of recovery significantly reduced hypoxia-ischemia-induced injury to immature rat brains and improved long-term memory and cognitive behavior. IGF-1's therapeutic effects likely involve its ability to prevent delayed apoptosis, as we demonstrated in primary cortical neuronal cultures under oxygen and glucose deprivation. IGF-1's neuroprotective effects parallel the activities of phosphatidylinositol-3/Akt and its down-stream signaling pathway, suggesting a potential mechanistic link. Overall, evidence from this investigation strongly supports IGF-1's potential therapeutic use in the treatment of hypoxic-ischemic encephalopathy in newborn patients.
Zhong
Jin
J
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Zhao
Limin
L
Du
Yansheng
Y
Wei
Gang
G
Yao
Wei-Guo
WG
Lee
Wei-Hua
WH
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000209:etiology / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000503:physiopathology* / Q000517:prevention & control; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D018782:Maze Learning / Q000187:drug effects; D008568:Memory; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects
D018696:Neuroprotective Agents; D007334:Insulin-Like Growth Factor I