title: Possible role of pannexin 1/P2x7 purinoceptor in neuroprotective mechanism of ischemic postconditioning in mice.
abstract: BACKGROUND
  Previous studies have suggested a significant role of pannexin 1 (Panx1)/P2X7 receptor complex in cardioprotective mechanism of ischemic preconditioning and postconditioning (IPC). The present study has been undertaken to investigate whether Panx1/P2X7 purinoceptors are also involved in the neuroprotective mechanism of IPC in mice.
  
  
  METHODS
  Bilateral carotid artery occlusion (BCAO) for 12 min followed by reperfusion for 24 h was used to produce ischemia-reperfusion-induced cerebral injury in Swiss albino mice. For IPC immediately after BCAO of 12 min, three cycles of 10-s ischemia and reperfusion each were given and then prolonged reperfusion of 24 h was used. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using a Morris water maze test. Rotarod test, inclined beam walking test, and neurologic severity score (NSS) were used to assess motor dysfunction. Acetylcholine esterase levels, brain thiobarbituric acid reactive species, and glutathione level were also estimated.
  
  
  RESULTS
  BCAO followed by reperfusion produced a significant increase in cerebral infarct size, NSS along with impairment of memory and motor dysfunction. It also increased brain acetylcholine esterase, thiobarbituric acid reactive species levels, and decreased the glutathione level. IPC produced a significant decrease in the cerebral infarct size and NSS along with reversal of ischemia-reperfusion-induced impairment of memory, motor dysfunction, and altered biochemical levels in the brain. IPC-induced neuroprotective effects were significantly abolished by pretreatment of mefloquine (15.0 mg/kg orally; 30.0 mg/kg orally), blocker of Panx1/P2X7 purinoceptor.
  
  
  CONCLUSIONS
  Therefore, activation of Panx1/P2X7 purinoceptors appears to play a significant role in the neuroprotective mechanism of IPC.
authors: CNS Research Laboratory, Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India.
authors: Namarta
authors: N
authors: Mahi
authors: CNS and CVS Research Laboratory, Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India.
authors: Amit
authors: A
authors: Kumar
authors: Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India.
authors: Amteshwar S
authors: AS
authors: Jaggi
authors: Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India. Electronic address: nirmal_puru@rediffmail.com.
authors: Nirmal
authors: N
authors: Singh
authors: Khalsa College of Pharmacy, Amritsar, Punjab, India.
authors: Ravi
authors: R
authors: Dhawan
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D017630:Connexins / Q000502:physiology*; D005260:Female; D057775:Ischemic Postconditioning; D008297:Male; D051379:Mice; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000502:physiology*; D058486:Receptors, Purinergic P2X7 / Q000502:physiology*
chemical_list: D017630:Connexins; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse; D058486:Receptors, Purinergic P2X7
keywords: Cerebral ischemia; Ischemic postconditioning; Neuroprotection; Panx1/P2X7