Longitudinal magnetic resonance imaging of sildenafil treatment of embolic stroke in aged rats

Stroke. 2011 Dec;42(12):3537-41. doi: 10.1161/STROKEAHA.111.622092. Epub 2011 Sep 8.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / pathology
  • Cerebrovascular Circulation / drug effects
  • Intracranial Embolism / drug therapy*
  • Intracranial Embolism / pathology
  • Longitudinal Studies
  • Magnetic Resonance Imaging*
  • Male
  • Neovascularization, Physiologic / drug effects*
  • Piperazines / pharmacology
  • Piperazines / therapeutic use*
  • Purines / pharmacology
  • Purines / therapeutic use
  • Rats
  • Rats, Wistar
  • Recovery of Function / drug effects
  • Sildenafil Citrate
  • Stroke / drug therapy*
  • Stroke / pathology
  • Sulfones / pharmacology
  • Sulfones / therapeutic use*
  • Vasodilator Agents / pharmacology
  • Vasodilator Agents / therapeutic use*

Substances

  • Piperazines
  • Purines
  • Sulfones
  • Vasodilator Agents
  • Sildenafil Citrate