Insulin-like growth factor-1 reduces postischemic white matter injury in fetal sheep.
Insulin-like growth factor-1 (IGF-1) is known to be important for oligodendrocyte survival and myelination. In the current study, the authors examined the hypothesis that exogenous IGF-1 could reduce postischemic white matter injury. Bilateral brain injury was induced in near-term fetal sheep by 30 minutes of reversible carotid artery occlusion. Ninety minutes after ischemia, either vehicle (n = 8) or a single dose of 3 microg IGF-1 (n = 9) was infused intracerebroventricularly over 1 hour. White matter changes were assessed after 4 days recovery in the parasagittal intragyral white matter and underlying corona radiata. Proteolipid protein (PLP) mRNA staining was used to identify bioactive oligodendrocytes. Glial fibrillary acidic protein (GFAP) and isolectin B-4 immunoreactivity were used to label astrocytes and microglia, respectively. Myelin basic protein (MBP) density and the area of the intragyral white matter tracts were determined by image analysis. Insulin-like growth factor-1 treatment was associated with significantly reduced loss of oligodendrocytes in the intragyral white matter (P < 0.05), with improved MBP density (P < 0.05), reduced tissue swelling, and increased numbers of GFAP and isolectin B-4 positive cells compared with vehicle treatment. After ischemia there was a close association of PLP mRNA labeled cells with reactive astrocytes and macrophages/microglia. In conclusion, IGF-1 can prevent delayed, postischemic oligodendrocyte cell loss and associated demyelination.
Guan
J
J
Research Center for Developmental Medicine and Biology, Department of Pediatrics, Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand.
Bennet
L
L
George
S
S
Wu
D
D
Waldvogel
H J
HJ
Gluckman
P D
PD
Faull
R L
RL
Crosier
P S
PS
Gunn
A J
AJ
D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D005315:Fetal Diseases / Q000188:drug therapy*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000627:therapeutic use*; D037102:Lectins / Q000032:analysis; D017628:Microglia / Q000737:chemistry / Q000473:pathology; D004676:Myelin Basic Protein / Q000032:analysis; D018991:Myelin Proteolipid Protein / Q000235:genetics; D009836:Oligodendroglia / Q000737:chemistry / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D015427:Reperfusion Injury / Q000517:prevention & control*; D012756:Sheep / Q000196:embryology; D020301:Vasospasm, Intracranial / Q000188:drug therapy*
D005904:Glial Fibrillary Acidic Protein; D037102:Lectins; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I