Longitudinal Magnetic Resonance Imaging of Sildenafil Treatment of Embolic Stroke in Aged Rats

Background and Purpose-Sildenafil provides restorative therapeutic benefits in the treatment of experimental stroke. The majority of experimental studies on treatment of stroke have been performed in young animals; however, stroke is primarily a disease of the aged. Thus, using MRI, we evaluated the effects of sildenafil treatment of embolic stroke in aged animals. Methods-Aged male Wistar rats (18 months) were subjected to embolic stroke and treated daily with saline (n = 10) or with sildenafil (n = 10) initiated at 24 hours and subsequently for 7 days after onset of ischemia. MRI measurements were performed at 24 hours and weekly to 6 weeks after embolization. Results-MRI and histological measurements demonstrated that sildenafil treatment of aged rats significantly enhanced angiogenesis and axonal remodeling after stroke compared to saline-treated aged rats. Local cerebral blood flow in the angiogenic area was elevated and expansion of the ipsilateral ventricle and, consequently, brain atrophy was significantly reduced in the sildenafil-treated rats. Conclusions-Treatment of embolic stroke in aged rats with sildenafil significantly augments angiogenesis and axonal remodeling, which increased local blood flow and reduced expansion of the ipsilateral ventricle 6 weeks after stroke compared to control aged rats. MRI can be used to investigate brain repair after stroke in aged rats. (Stroke. 2011;42:3537-3541.)