title: Neuroprotective efficacy of subcutaneous insulin-like growth factor-I administration in normotensive and hypertensive rats with an ischemic stroke.
abstract: The aim of this study was to test the insulin-like growth factor-I (IGF-I) as a neuroprotective agent in a rat model for ischemic stroke and to compare its neuroprotective effects in conscious normotensive and spontaneously hypertensive rats. The effects of subcutaneous IGF-I injection were investigated in both rat strains using the endothelin-1 rat model for ischemic stroke. Motor-sensory functions were measured using the Neurological Deficit Score. Infarct size was assessed by Cresyl Violet staining. Subcutaneous administration of IGF-I resulted in significantly reduced infarct volumes and an increase in motor-sensory functions in normotensive rats. In these rats, IGF-I did not modulate blood flow in the striatum and had no effect on the activation of astrocytes as assessed by GFAP staining. In hypertensive rats, the protective effects of IGF-I were smaller and not always significant. Furthermore, IGF-I significantly reduced microglial activation in the cortex of hypertensive rats, but not in normotensive rats. More detailed studies are required to find out whether the reduction by IGF-I of microglial activation contributes to an impairment IGF-I treatment efficacy. Indeed, we have shown before that microglia in hypertensive rats have different properties compared to those in control rats, as they exhibit a reduced responsiveness to ischemic stroke and lipopolysaccharide.
authors.affiliation: Center for Neurosciences, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, Brussels, Belgium; Department of Pharmacology, VUB Brussel, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: De Geyter
authors.forename: W
authors.initials: W
authors.lastname: Stoop
authors.forename: S
authors.initials: S
authors.lastname: Sarre
authors.forename: J
authors.initials: J
authors.lastname: De Keyser
authors.forename: R
authors.initials: R
authors.lastname: Kooijman
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D019332:Endothelin-1 / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology*; D017078:Laser-Doppler Flowmetry; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D017628:Microglia / Q000187:drug effects; D009422:Nervous System Diseases / Q000503:physiopathology / Q000523:psychology; D018696:Neuroprotective Agents; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011994:Recombinant Proteins / Q000494:pharmacology; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D013686:Telemetry
chemical_list: D019332:Endothelin-1; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D005947:Glucose
keywords: 3-aminopropyltriethoxylane; APES; Et-1; GFAP; IFN; IGF-I; IL; MCAO; NDS; NIH; National Institute of Health; PBS; SEM; SHRs; TNF; VUB; Vrije Universiteit Brussel; brain ischemia; endothelin-1; glial fibrillary acidic protein; hypertension; insulin-like growth factor-I; interferon; interleukin; middle cerebral artery occlusion; neuroglia; neurological deficit score; phosphate-buffered saline; spontaneously hypertensive rats; standard error of mean; tumor necrosis factor