Intracerebral transportation and cellular localisation of insulin-like growth factor-1 following central administration to rats with hypoxic–ischemic brain injury
| Autor: | Stephen J. M. Skinner, Chris E. Williams, Erica J. Beilharz, Peter D. Gluckman, Jian Guan |
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| Rok vydání: | 2000 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Central nervous system Ischemia Tritium Neuroprotection White matter Insulin-like growth factor Internal medicine medicine Animals Tissue Distribution Insulin-Like Growth Factor I Rats Wistar Perivascular space Molecular Biology Injections Intraventricular Neurons Pia mater business.industry General Neuroscience Brain Biological Transport medicine.disease Immunohistochemistry Rats Insulin-Like Growth Factor Binding Protein 2 medicine.anatomical_structure Endocrinology Hypoxia-Ischemia Brain Cerebral ventricle Autoradiography Neurology (clinical) business Developmental Biology |
| Zdroj: | Brain Research. 853:163-173 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/s0006-8993(99)02030-2 |
| Popis: | 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 (p0.05). 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 (p0.05). 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. |
| Databáze: | OpenAIRE |
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