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

Insulin-like growth factor-1 (IGF-1) has been shown to be neuroprotective w hen administered centrally following hypoxic-ischemic (HI) brain injury. Ho wever, the cerebral distribution and site of action of IGF-1 after intracer ebroventricular (i.c.v.) administration are not known. A unilateral HI brai n injury was induced in adult rats by a modified Levine method. Either H-3- 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 u sing image analysis. The regional distribution and cellular localisation of H-3-IGF-1 were examined autoradiographically in potentially injured hemisp heres at 0.5 and 6 h after administration. Tritiated IGF-1 was detected pre dominantly in the pia mater, perivascular spaces and subcortical white matt er tracts 0.5 h after administration and decreased by 6 h (p < 0.05). The s ignals associated with the perivascular spaces and pia mater were not block ed by unlabelled IGF-1, suggesting non-saturable binding in these brain are as. IGF-1 signal was co-localised with IGF binding protein (IGFBP)-2 immuno staining in the white matter tracts where the signal was blocked by unlabel led 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 administr ation, suggesting specific and persistent binding to these cells. Our resul ts indicate that centrally administered IGF-1 can be translocated to neuron s and glia via the perivascular circulation and the ependymal cell-white ma tter tract pathways. (C) 2000 Elsevier Science B.V. All rights reserved.