HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Sildenafil improves epicenter vascular perfusion but not hindlimb functional recovery after contusive spinal cord injury in mice.

Abstract
Nitric oxide (NO) is an important regulator of vasodilation and angiogenesis in the central nervous system (CNS). Signaling initiated by the membrane receptor CD47 antagonizes vasodilation and angiogenesis by inhibiting synthesis of cyclic guanosine monophosphate (cGMP). We recently found that deletion of CD47 led to significant functional locomotor improvements, enhanced angiogenesis, and increased epicenter microvascular perfusion in mice after moderate contusive spinal cord injury (SCI). We tested the hypothesis that improving NO/cGMP signaling within the spinal cord immediately after injury would increase microvascular perfusion, angiogenesis, and functional recovery, with an acute, 7-day administration of the cGMP phosphodiesterase 5 (PDE5) inhibitor sildenafil. PDE5 expression is localized within spinal cord microvascular endothelial cells and smooth muscle cells. While PDE5 antagonism has been shown to increase angiogenesis in a rat embolic stroke model, sildenafil had no significant effect on angiogenesis at 7 days post-injury after murine contusive SCI. Sildenafil treatment increased cGMP concentrations within the spinal cord and improved epicenter microvascular perfusion. Basso Mouse Scale (BMS) and Treadscan analyses revealed that sildenafil treatment had no functional consequence on hindlimb locomotor recovery. These data support the hypothesis that acutely improving microvascular perfusion within the injury epicenter by itself is an insufficient strategy for improving functional deficits following contusive SCI.
AuthorsScott A Myers, William H DeVries, Mark J Gruenthal, Kariena R Andres, Theo Hagg, Scott R Whittemore
JournalJournal of neurotrauma (J Neurotrauma) Vol. 29 Issue 3 Pg. 528-38 (Feb 10 2012) ISSN: 1557-9042 [Electronic] United States
PMID21970599 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Phosphodiesterase 5 Inhibitors
  • Piperazines
  • Purines
  • Sulfones
  • Nitric Oxide
  • Sildenafil Citrate
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Cyclic GMP
Topics
  • Animals
  • Antigens, CD (metabolism)
  • Antigens, Differentiation, Myelomonocytic (metabolism)
  • Capillaries (metabolism)
  • Cyclic GMP (physiology)
  • Cyclic Nucleotide Phosphodiesterases, Type 5 (biosynthesis)
  • Endothelial Cells (metabolism)
  • Female
  • Hindlimb (blood supply, drug effects)
  • Image Processing, Computer-Assisted
  • Immunoenzyme Techniques
  • Immunohistochemistry
  • Locomotion (physiology)
  • Mice
  • Mice, Inbred C57BL
  • Microcirculation (physiology)
  • Nitric Oxide (physiology)
  • Phosphodiesterase 5 Inhibitors (pharmacology)
  • Piperazines (therapeutic use)
  • Purines (therapeutic use)
  • Recovery of Function (drug effects)
  • Regional Blood Flow (drug effects)
  • Sildenafil Citrate
  • Spinal Cord Injuries (drug therapy, physiopathology)
  • Sulfones (therapeutic use)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: