Jan 30, 2014

Sildenafil mediates blood-flow redistribution and neuroprotection after neonatal hypoxia-ischemia

Stroke; a Journal of Cerebral Circulation
Christiane Charriaut-MarlangueOlivier Baud

Abstract

The best conceivable treatment for hypoxia-ischemia (HI) is the restoration of blood flow to the hypoxic-ischemic region(s). Our objective was to examine whether boosting NO-cGMP signaling using sildenafil citrate, a phosphodiesterase-type 5 inhibitor, could modify cerebral blood flow and reduce lesions in the developing brain. HI was induced in P7 Sprague-Dawley rats by unilateral carotid artery occlusion and hypoxia, and followed by either PBS or sildenafil. Blood-flow velocities were measured by ultrasound imaging with sequential Doppler recordings to evaluate collateral recruitment. Cell death, blood-brain barrier integrity, and glial activation were analyzed by immunohistochemistry. Motor behavior was evaluated using an open-field device adapted to neonatal animals. Sildenafil citrate (10 mg/kg) induced collateral patency, reduced terminal dUTP nick-end labeling-positive cells, reactive astrogliosis, and macrophage/microglial activation at 72 hours and 7 days post-HI. Sildenafil also reduced the number of terminal dUTP nick-end labeling-positive endothelial cells within lesion site. Seven days after HI and sildenafil treatment, tissue loss was significantly reduced, and animals recovered motor coordination. Our findings st...Continue Reading

  • References33
  • Citations18

Mentioned in this Paper

Ischemia
Cerebral Blood Flow Imaging
Blood - Brain Barrier Anatomy
Phosphodiesterase Inhibitors
Immunohistochemistry
Hypoxia-Ischemia, Brain
Phosphoric diester hydrolase
Piperazines
Diastolic Blood Pressure
Neuroprotection

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