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.

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.