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.

MATERIALS AND 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: Namarta Mahi, Amit Kumar, Amteshwar S Jaggi, Nirmal Singh, Ravi Dhawan
• Journal: The Journal of surgical research (J Surg Res) Vol. 196 Issue 1 Pg. 190-9 (Jun 01 2015) ISSN: 1095-8673 [Electronic] United States
• PMID: 25796110 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Connexins
• Nerve Tissue Proteins
• Panx1 protein, mouse
• Receptors, Purinergic P2X7

Topics

• Animals
• Brain Ischemia (physiopathology)
• Connexins (physiology)
• Female
• Ischemic Postconditioning
• Male
• Mice
• Motor Activity
• Nerve Tissue Proteins (physiology)
• Receptors, Purinergic P2X7 (physiology)