Selective neuroprotective effects with insulin-like growth factor-1 in phenotypic striatal neurons following ischemic brain injury in fetal sheep
| Autor: | Peter D. Gluckman, S. George, Jian Guan, Richard L.M. Faull, H Keunen, Henry J. Waldvogel, Alistair J. Gunn, Laura Bennet |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Calbindins medicine.medical_treatment Central nervous system Striatum Nitric Oxide Synthase Type I Biology Neuroprotection Brain Ischemia Choline O-Acetyltransferase Insulin-like growth factor Neurochemical Fetus S100 Calcium Binding Protein G Internal medicine Basal ganglia medicine Animals Neuropeptide Y Insulin-Like Growth Factor I Neurons Sheep Glutamate Decarboxylase General Neuroscience medicine.disease Immunohistochemistry Corpus Striatum Perinatal asphyxia medicine.anatomical_structure Endocrinology Neuroprotective Agents Parvalbumins Phenotype nervous system Cholinergic Nitric Oxide Synthase |
| Zdroj: | Neuroscience. 95(3) |
| ISSN: | 0306-4522 |
| Popis: | Severe perinatal asphyxia can lead to injury and dysfunction of the basal ganglia. Post insult administration of insulin-like growth factor-1 is neuroprotective, particularly in the striatum. Insulin-like growth factor-1 is also known to be a neuromodulator of several types of striatal neurons. The striatum comprises various phenotypic neurons with a complex neurochemical anatomy and physiology. In the present study, we examined the specificity of neuronal rescue with insulin-like growth factor-1 on different striatal neurons. Bilateral brain injury was induced in near term fetal sheep by 30 min of reversible carotid artery occlusion. A single dose of 3 microg of insulin-like growth factor-1 was infused over 1 h into the lateral ventricle 90 min following ischemia. The histological and immunohistochemical outcome were examined after 4 days recovery using paraffin tissue preparations. Insulin-like growth factor-1 treatment (n = 11) significantly reduced the percentage of neuronal loss in the striatum compared with the vehicle treated group (n = 10, 28.3+/-5.1% vs 55.5+/-17.3%, P0.005). Immunohistochemical studies showed that ischemia resulted in a significant loss of calbindin-28kd, choline acetyltransferase, parvalbumin, glutamate acid decarboxylase, neuronal nitric oxide synthase and neuropeptide Y immunopositive neurons, compared with sham controls. Insulin-like growth factor-1 markedly prevented the loss of calbindin-28kd (n = 7, P0.05), choline acetyltransferase (n = 7, P0.05), neuropeptide Y (n = 7, P0.05), neuronal nitric oxide synthase (n = 8, P0.05) and glutamate acid decarboxylase (n = 9, P0.05) immunopositive neurons, but failed to protect parvalbumin (n = 6) immunopositive neurons. The present study indicates that the therapeutic effect of insulin-like growth factor-1 in the basal ganglia is selectively associated with cholinergic and some phenotypic GABAergic neurons. These data suggest a potential role for insulin-like growth factor-1 in preventing cerebral palsy due to perinatal asphyxia. |
| Databáze: | OpenAIRE |
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