title: Neuroprotective effect of tadalafil, a PDE-5 inhibitor, and its modulation by L-NAME in mouse model of ischemia-reperfusion injury.
abstract: BACKGROUND
  The present study investigates the neuroprotective effect of tadalafil, a selective phosphodiesterase-5 inhibitor, in a mouse model of ischemia-reperfusion injury.
  
  
  METHODS
  Bilateral carotid artery occlusion for 12 min followed by reperfusion for 24 h was employed to produce ischemia-reperfusion-induced cerebral injury in male Swiss mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using Morris water maze test. Degree of motor incoordination was evaluated using inclined beam walk test, rota-rod test, and lateral push test. Brain nitrite/nitrate, brain acetylcholinesterase activity, brain thiobarbituric acid reactive species, and glutathione levels were also estimated.
  
  
  RESULTS
  Bilateral carotid artery occlusion, followed by reperfusion, produced a significant rise in cerebral infarct size, brain nitrite/nitrate levels, acetylcholinesterase activity, and thiobarbituric acid reactive species level along with a fall in glutathione. A significant impairment of memory and motor coordination was also noted. Pretreatment of tadalafil significantly attenuated the above effects of ischemia-reperfusion injury. Tadalafil-induced neuroprotective effects were significantly attenuated by administration of L-NAME, a nonselective nitric oxide synthase inhibitor.
  
  
  CONCLUSIONS
  Results indicate that tadalafil exerts neuroprotective effects, probably through nitric oxide-dependent pathways. Therefore, phosphodiesterase-5 can be explored as an important target to contain ischemia-reperfusion injury.
authors.affiliation: Pharmacology Division, Department of Pharmaceutical sciences & Drug Research, Punjabi University, Patiala, Punjab, India.
authors.forename: Puja
authors.initials: P
authors.lastname: Gulati
authors.forename: Nirmal
authors.initials: N
authors.lastname: Singh
mesh_terms: D000818:Animals; D002243:Carbolines / Q000494:pharmacology* / Q000627:therapeutic use; D002544:Cerebral Infarction / Q000188:drug therapy*; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000517:prevention & control*; D000068581:Tadalafil
chemical_list: D002243:Carbolines; D018696:Neuroprotective Agents; D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil; D019331:NG-Nitroarginine Methyl Ester
keywords: Cerebral ischemia; L-NAME; Memory; Neuroprotection; Nitric oxide; Tadalafil