Tadalafil enhances the neuroprotective effects of ischemic postconditioning in mice, probably in a nitric oxide associated manner.
This study investigates the modulatory effect of tadalafil, a selective phosphodiesterase (PDE-5) inhibitor, on the neuroprotective effects of ischemic postconditioning (iPoCo) in mice. Bilateral carotid artery occlusion (BCAO) for 12 min followed by reperfusion for 24 h was employed to produce ischemia and reperfusion induced cerebral injury. Cerebral infarct size was measured using TTC staining. Memory was assessed using the Morris water maze test. Degree of motor incoordination was evaluated using inclined beam-walking, rota-rod, and lateral push tests. Brain nitrite/nitrate, acetylcholinesterase activity, TBARS, and glutathione levels were also estimated. BCAO followed by reperfusion produced a significant increase in cerebral infarct size, brain nitrite/nitrate and TBARS levels, and acetylcholinesterase activity along with a reduction in glutathione. Marked impairment of memory and motor coordination was also noted. iPoCo consisting of 3 episodes of 10 s carotid artery occlusion and reperfusion instituted immediately after BCAO significantly decreased infarct size, memory impairment, motor incoordination, and altered biochemistry. Pretreatment with tadalafil mimicked the neuroprotective effects of iPoCo. The tadalafil-induced neuroprotective effects were significantly attenuated by l-NAME, a nonselective NOS inhibitor. We concluded that tadalafil mimics the neuroprotective effects of iPoCo, probably through a nitric oxide dependent pathway, and PDE-5 could be a target of interest with respect to the neuroprotective mechanism of iPoCo.
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
Puja
P
Gulati
Nirmal
N
Singh
D000818:Animals; D001259:Ataxia / Q000188:drug therapy / Q000523:psychology; D001921:Brain / Q000098:blood supply / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002243:Carbolines / Q000627:therapeutic use*; D002544:Cerebral Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism; D057775:Ischemic Postconditioning; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000523:psychology; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000068581:Tadalafil
D002243:Carbolines; D018696:Neuroprotective Agents; D058986:Phosphodiesterase 5 Inhibitors; D009569:Nitric Oxide; D000068581:Tadalafil; D019001:Nitric Oxide Synthase; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D019331:NG-Nitroarginine Methyl Ester