Intranasal delivery of erythropoietin plus insulin-like growth factor–I for acute neuroprotection in stroke
| Autor: | Shane Sprague, Murat Digicaylioglu, Augusto Parra, Sanjivan Kohli, Robert A. Scranton, David Jiménez, Lauren Fletcher, Stuart A. Lipton |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Ischemia Pharmacology Neuroprotection Iodine Radioisotopes Mice Insulin-like growth factor Drug Delivery Systems Animals Medicine Insulin-Like Growth Factor I Erythropoietin Stroke Administration Intranasal business.industry Growth factor Infarction Middle Cerebral Artery General Medicine medicine.disease Surgery Mice Inbred C57BL Disease Models Animal Neuroprotective Agents Cytokine Acute Disease Drug Therapy Combination Nasal administration business medicine.drug |
| Zdroj: | Journal of Neurosurgery. 111:164-170 |
| ISSN: | 1933-0693 0022-3085 |
| DOI: | 10.3171/2009.2.jns081199 |
| Popis: | Object Individually, the cytokines erythropoietin (EPO) and insulin-like growth factor–I (IGF-I) have both been shown to reduce neuronal damage significantly in rodent models of cerebral ischemia. The authors have previously shown that EPO and IGF-I, when administered together, provide acute and prolonged neuroprotection in cerebrocortical cultures against N-methyl-d-aspartate–induced apoptosis. The aim of this study was to determine whether intranasally applied EPO plus IGF-I can provide acute neuroprotection in an animal stroke model and to show that intranasal administration is more efficient at delivering EPO plus IGF-I to the brain when compared with intravenous, subcutaneous, or intraperitoneal administration. Methods The EPO and IGF-I were administered intranasally to mice that underwent transient middle cerebral artery occlusion (MCAO). Stroke volumes were measured after 1 hour of MCAO and 24 hours of reperfusion. To evaluate the long-term effects of this treatment, behavioral outcomes were assessed at 3, 30, 60, and 90 days following MCAO. Radiography and liquid scintillation were used to visualize and quantify the uptake of radiolabeled 125I-EPO and 125I–IGF-I into the mouse brain after intranasal, intravenous, subcutaneous, or intraperitoneal administration. Results Intranasal administration of EPO plus IGF-I reduced stroke volumes within 24 hours and improved neurological function in mice up to 90 days after MCAO. The 125I-EPO and 125I–IGF-I were found in the brain within 20 minutes after intranasal administration and accumulated within the injured areas of the brain. In addition, intranasal administration delivered significantly higher levels of the applied 125I-EPO and 125I–IGF-I to the brain compared with intravenous, subcutaneous, or intraperitoneal administration. Conclusions The data demonstrate that intranasal EPO plus IGF-I penetrates into the brain more efficiently than other drug delivery methods and could potentially provide a fast and efficient treatment to prevent chronic effects of stroke. |
| Databáze: | OpenAIRE |
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