NeuropharmacologyModulation of the balance between cannabinoid CB1 and CB2 receptor activation during cerebral ischemic/reperfusion injury
Section snippets
Animals and surgical procedures
The cerebral ischemia/reperfusion studies were carried out in 8-week-old male C57BL/6 mice (weighing 23–27 g; Taconic, Hudson, NY, USA) and conducted in accordance with the guidelines approved by the Institutional Animal Care and Use Committee at Temple University and followed the National Institutes of Health Guide for the Care and Use of Laboratory Animals. All efforts were made to minimize the number of animals used and their suffering.
Middle cerebral artery occlusion and reperfusion (MCAO/R)
The animals were anesthetized by i.p. injection of a
CB1 and CB2 mRNA expression in brain during MCAO
There were no differences in CB1 mRNA expression in the non-ischemic hemisphere compared with normal control at 1, 3, 6 and 24 h after MCAO. CB1 expression in the ischemic hemisphere increased at 1 h after ischemia and was maximal at 6 h. Similarly there were no significant differences in CB2 mRNA expression in the non-ischemic hemispheres compared with control. However, CB2 expression in the ischemic hemispheres decreased during first 3 h following ischemia, followed by a gradual increase
Discussion
The primary goal of this study was to investigate whether modification of the endocannabinoid system could influence outcome following cerebral ischemia/reperfusion injury. The hypothesis that modification of the endocannabinoid system could influence outcome following ischemia was based upon prior reports that this system can have direct effects on neuronal function and can also modify inflammatory responses (Baker et al 2001, van der Stelt et al 2001, Muthian et al 2004, McCollum et al 2007).
Conclusion
In conclusion, the results of this investigation demonstrate dynamic changes in the expression of CB1 and CB2 receptors during cerebral ischemic/reperfusion injury in mice. The effects of stimulation of these receptors on damage ischemia/reperfusion injury differed dramatically. Stimulation of the CB2 receptor was found to be neuroprotective, while inhibition of the CB1 receptor was also protective. The combination of a CB2 agonist and a CB1 antagonist provided the greatest degree of protection
Acknowledgments
This project is funded, in part, under a grant with the Pennsylvania Department of Health, a contract from BTG (London) and grants from DA P30 13429, DA 03672 and DA 05488 from the National Institute on Drug Abuse.
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