Abstract
Deborah De Geyter1,Wendy Stoop1, Sophie Sarre2 and Ron Kooijman1
1Department of Pharmacology and 2Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Brussels, 1090, Belgium (Center for Neuroscience)
Background: The main goal of this study was to test IGF-I, a pleiotropic peptide, for the treatment of ischemic stroke in an animal model. To facilitate translation to the clinic, we have developed a rat model for preclinal studies in conscious animals in the presence of a co-morbidity factor. We chose to work with hypertensive rats since hypertension is an important modifiable risk factor for stroke which influences the clinical outcome. We aimed to compare the susceptibility to ischemia of hypertensive rats with those of normotensive controls in a rat model for induction of ischemic stroke in conscious animals. Methods: The vasoconstrictor endothelin-1 was stereotactically applied in the vicinity of the middle cerebral artery of conscious control Wistar Kyoto rats (WKYRs) and Spontaneously Hypertensive rats (SHRs). Infarct size was assessed histologically by cresylviolet staining. Sensory-motor functions were measured using the Neurological Deficit Score. Activation of microglia/macrophages in the striatum and cortex was investigated by immunohistochemistry using antibodies against CD68 and Iba-1. IGF-I was administered systemically (subcutaneously or intravenously) in a dose of 300 and 900 µg. Results and conclusions: In the Et-1 rat model, we found that the SHRs displayed 50% less activated microglia. These results were confirmed in the lipopolyssacharide model for neuroinflammation indicating that microglia in SHRs were less susceptible for microglial/phagocytic activation compared to their normotensive counterparts. Systemic administration of IGF-I resulted in lower infarct volumes and better NDSs in the WKYRs indicating that IGF-I administration could become an effective therapy for ischemic stroke. In the SHRs however, the effects of IGF-I were smaller, maybe due differences in vasculature or different responses of microglial cells. Ongoing research to the differences between normotensive en hypertensive rats may provide indications for optimizing the effects of IGF-I in hypertensive rats.
1Department of Pharmacology and 2Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Brussels, 1090, Belgium (Center for Neuroscience)
Background: The main goal of this study was to test IGF-I, a pleiotropic peptide, for the treatment of ischemic stroke in an animal model. To facilitate translation to the clinic, we have developed a rat model for preclinal studies in conscious animals in the presence of a co-morbidity factor. We chose to work with hypertensive rats since hypertension is an important modifiable risk factor for stroke which influences the clinical outcome. We aimed to compare the susceptibility to ischemia of hypertensive rats with those of normotensive controls in a rat model for induction of ischemic stroke in conscious animals. Methods: The vasoconstrictor endothelin-1 was stereotactically applied in the vicinity of the middle cerebral artery of conscious control Wistar Kyoto rats (WKYRs) and Spontaneously Hypertensive rats (SHRs). Infarct size was assessed histologically by cresylviolet staining. Sensory-motor functions were measured using the Neurological Deficit Score. Activation of microglia/macrophages in the striatum and cortex was investigated by immunohistochemistry using antibodies against CD68 and Iba-1. IGF-I was administered systemically (subcutaneously or intravenously) in a dose of 300 and 900 µg. Results and conclusions: In the Et-1 rat model, we found that the SHRs displayed 50% less activated microglia. These results were confirmed in the lipopolyssacharide model for neuroinflammation indicating that microglia in SHRs were less susceptible for microglial/phagocytic activation compared to their normotensive counterparts. Systemic administration of IGF-I resulted in lower infarct volumes and better NDSs in the WKYRs indicating that IGF-I administration could become an effective therapy for ischemic stroke. In the SHRs however, the effects of IGF-I were smaller, maybe due differences in vasculature or different responses of microglial cells. Ongoing research to the differences between normotensive en hypertensive rats may provide indications for optimizing the effects of IGF-I in hypertensive rats.
| Original language | English |
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| Title of host publication | Belgian Society of Fundamental and Clinical Physiology and Pharmacology; Spring Meeting (Brussel). Orale presentatie. |
| Publication status | Published - 16 Mar 2012 |
| Event | Belgian Society of Fundamental and Clinical Physiology and Pharmacology; Spring Meeting (Brussel). Orale presentatie. - Brussels, Belgium Duration: 16 Mar 2013 → … |
Conference
| Conference | Belgian Society of Fundamental and Clinical Physiology and Pharmacology; Spring Meeting (Brussel). Orale presentatie. |
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| Country/Territory | Belgium |
| City | Brussels |
| Period | 16/03/13 → … |