Intracerebral transportation and cellular localisation of insulin-like growth factor-1 following central administration to rats with hypoxic-ischemic brain injury.

Abstract

Insulin-like growth factor-1 (IGF-1) has been shown to be neuroprotective when administered centrally following hypoxic-ischemic (HI) brain injury. However, the cerebral distribution and site of action of IGF-1 after intracerebroventricular (i.c.v.) administration are not known. A unilateral HI brain injury was induced in adult rats by a modified Levine method. Either 3H-IGF-1 alone, or in combination with unlabelled IGF-1, was administered into the lateral ventricle 2 h after injury. The activity of 3H-IGF-1 signal in the potentially injured cortex was compared between two treatment groups using image analysis. The regional distribution and cellular localisation of 3H-IGF-1 were examined autoradiographically in potentially injured hemispheres at 0.5 and 6 h after administration. Tritiated IGF-1 was detected predominantly in the pia mater, perivascular spaces and subcortical white matter tracts 0.5 h after administration and decreased by 6 h (p<0.05). The signals associated with the perivascular spaces and pia mater were not blocked by unlabelled IGF-1, suggesting non-saturable binding in these brain areas. IGF-1 signal was co-localised with IGF binding protein (IGFBP)-2 immunostaining in the white matter tracts where the signal was blocked by unlabelled IGF-1, suggesting competitive association. IGF-1 signal associated with neurons and glia was maximal in the cerebral cortex and less in the CA1-2 subregion of the hippocampus which were blocked by unlabelled IGF-1 (p<0.05). The signals from cortical neurons did not decrease 6 h after administration, suggesting specific and persistent binding to these cells. Our results indicate that centrally administered IGF-1 can be translocated to neurons and glia via the perivascular circulation and the ependymal cell-white matter tract pathways.

• Authors: J Guan, E J Beilharz, S J Skinner, C E Williams, P D Gluckman
• Journal: Brain research (Brain Res) Vol. 853 Issue 2 Pg. 163-73 (Jan 24 2000) ISSN: 0006-8993 [Print] Netherlands
• PMID: 10640614 (Publication Type: Journal Article)

Chemical References

• Insulin-Like Growth Factor Binding Protein 2
• Tritium
• Insulin-Like Growth Factor I

Topics

• Animals
• Autoradiography
• Biological Transport (drug effects)
• Brain (metabolism, pathology)
• Hypoxia-Ischemia, Brain (metabolism)
• Immunohistochemistry
• Injections, Intraventricular
• Insulin-Like Growth Factor Binding Protein 2 (metabolism)
• Insulin-Like Growth Factor I (administration & dosage, metabolism, pharmacokinetics)
• Male
• Neurons (cytology, metabolism)
• Rats
• Rats, Wistar
• Tissue Distribution
• Tritium