Intracerebroventricular injection of epidermal growth factor reduces neurological deficit and infarct volume and enhances nestin expression following focal cerebral infarction in adult hypertensive rats

Abstract

Studies have documented the proliferative effects of epidermal growth factor (EGF) on neural progenitor cells in the normal or injured brain. The effect of EGF on post-stroke cerebral expression of nestin, a marker of neural progenitor cells, has not been examined in hypertensive rats. In the present study, adult renovascular hypertensive Sprague-Dawley rats underwent either real or sham middle cerebral artery occlusion (MCAO). Intracerebroventricular injections of either 1 g EGF or vehicle (0.01 mol/L phosphate-buffered saline containing 0.1 mg/mL rat serum albumin) were made 24 and 48 h after MCAO. Then, 1, 2, 3 and 4 weeks after MCAO, the postural reflex was evaluated in a blinded fashion before rat brains were processed to determine the infarct volume plus immunoreactivity for nestin and/or glial fibrillary acidic protein (GFAP). Another group of rats was used to quantify nestin expression using western blot analysis. Middle cerebral artery occlusion resulted in a focal infarct that was largest at 1 week and diminished gradually over the time. The impaired postural reflex followed a similar time-course. In addition, MCAO induced a marked increase in nestin expression in both hemispheres, with a higher expression in the right hemisphere; this change was maximal at 1 week and largely subsided at 3 or 4 weeks. Within the right hemisphere, nestin expression was most pronounced in the subventricular and peri-infarct zones. Most nestin-immunoreactive cells were also positive for GFAP. Thus, EGF treatment significantly increases nestin expression, reduces infarct volume and ameliorates postural reflex impairment in adult hypertensive rats. © 2008 Blackwell Publishing Asia Pty Ltd.