This study was designed to determine the potential of IGF-1 as a neuronal rescue agent after cerebral ischemia. Unanesthetized late gestation fetal sheep were subjected to 30-min cerebral ischemia by inflation of carotid artery occluder cuffs. 2 h later either 0.1 microgram rhIGF-1, 1 microgram rhIGF-1, 10 micrograms rhIGF-1, or vehicle was infused into a lateral cerebral ventricle over 1 h. Histologic outcome was assessed 5 d later. Overall neuronal loss was reduced with 0.1 microgram (P < 0.05) and 1 microgram (P < 0.002) rhIGF-1, but treatment with 10 micrograms was not effective. With 1 microgram rhIGF-1 neuronal loss scores were significantly lower in brain regions examined including cortex, hippocampus, and striatum, whereas with 0.1 microgram rhIGF-1 the parietal cortex and thalamus were not improved and the improvement seen in other regions was less than with 1 microgram rhIGF-1. Treatment with 1 microgram rhIGF-1 also delayed the onset of seizures and reduced their incidence. Moreover, the secondary phase of cytotoxic edema was reduced and delayed in onset. We conclude that low dose rhIGF-1 therapy promotes neuronal rescue after cerebral hypoxic-ischemic injury in utero, but the effect is dose dependent. Importantly, rhIGF-1 is effective and nontoxic when administered 2 h after the hypoxic ischemic insult. This distinguishes IGF-1 from most other neuroprotective therapies and suggests clinical application may be possible.
B M Johnston, E C Mallard, C E Williams, P D Gluckman
Title and authors | Publication | Year |
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Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs
AJ Gunn, TR Gunn, HH de Haan, CE Williams, PD Gluckman |
Journal of Clinical Investigation | 1997 |
Vasoactive intestinal peptide prevents excitotoxic cell death in the murine developing brain
P Gressens, S Marret, JM Hill, DE Brenneman, I Gozes, M Fridkin, P Evrard |
Journal of Clinical Investigation | 1997 |
The Spatial and Temporal Distribution of Insulin-Like Growth Factor-1 Following Experimental Myocardial Infarction in the Rat
RV MApplSc, LM PhD, NS PhD, JB DSc, PD DSc, BM DPhil |
Cardiovascular Pathology | 1997 |
Ethanol Promotes Cell Death by Inhibition of the Insulin-Like Growth Factor I Receptor
S Cui, M Tewari, T Schneider, R Rubin |
Alcoholism, clinical and experimental research | 1997 |
The effect of insulin-like growth factors on brain myelination and their potential therapeutic application in myelination disorders
W Zumkeller |
European Journal of Paediatric Neurology | 1997 |
Brief Repeated Umbilical Cord Occlusions Cause Sustained Cytotoxic Cerebral Edema and Focal Infarcts in Near-Term Fetal Lambs
HH de Haan, AJ Gunn, CE Williams, PD Gluckman |
Pediatric Research | 1997 |
Amyloid precursor protein requires the insulin signaling pathway for neurotrophic activity
WC Wallace, CA Akar, WE Lyons, HK Kole, JM Egan, B Wolozin |
Molecular Brain Research | 1997 |
Insulin-like growth factor-I (IGF-I) immunoreactivity in the Alzheimer's disease temporal cortex and hippocampus
B Connor, EJ Beilharz, C Williams, B Synek, PD Gluckman, RL Faull, M Dragunow |
Molecular Brain Research | 1997 |
rhIGF-I administration in humans: differential metabolic effects of bolus vs. continuous subcutaneous delivery
N Mauras, PM Martha, V Quarmby, MW Haymond |
American journal of physiology. Endocrinology and metabolism | 1997 |
Plasma Insulin-like Growth Factor I and IGF Binding Protein 3 Levels in Patients With Acute Cerebral Ischemic Injury
S Schwab, M Spranger, S Krempien, W Hacke, M Bettendorf |
Stroke; a journal of cerebral circulation | 1997 |
Selective expression of insulin-like growth factor II in the songbird brain
M Holzenberger, E D Jarvis, C Chong, M Grossman, F Nottebohm, C Scharff |
The Journal of neuroscience : the official journal of the Society for Neuroscience | 1997 |
Selective Expression of Insulin-Like Growth Factor II in the Songbird Brain
Holzenberger M, Jarvis ED, Chong C, Grossman M, Nottebohm F, Scharff C |
Journal of Neuroscience | 1997 |