Format

Send to

Choose Destination
Neurosci Lett. 2014 May 21;569:104-9. doi: 10.1016/j.neulet.2014.03.077. Epub 2014 Apr 12.

The cannabinoid CB2 receptor agonist GW405833 does not ameliorate brain damage induced by hypoxia-ischemia in rats.

Author information

1
Department of Pharmacology and Toxicology, School of Medical Sciences, and the Brain Health Research Centre, University of Otago, P.O. Box 913, Dunedin, New Zealand.
2
Department of Pharmacology and Toxicology, School of Medical Sciences, and the Brain Health Research Centre, University of Otago, P.O. Box 913, Dunedin, New Zealand. Electronic address: john.ashton@otago.ac.nz.

Erratum in

  • Neurosci Lett. 2014 Jun 20;572:19.

Abstract

The cannabinoid CB2 receptor has been under investigation as a potential target for neuroprotection with the suppression of neuroinflammation as the proposed mechanism of action. Several studies have now reported that CB2 agonists are neuroprotective in models of cerebral ischemia. However, these studies have tended to measure brain infarctions in rodents 1-3 days after drug administration and have not assessed behavioral outcomes. As it has been shown that apparent protection soon after injury is not necessarily correlated with improved outcome after several weeks, we tested the CB2 selective agonist GW405833 in a model of cerebral hypoxia-ischemia, and assessed histological and behavioral outcomes 15 days after injury. Many putatively neuroprotective drugs have failed to translate from promising preclinical results to clinical success. We designed our experiments to not only stringently test CB2 mediated neuroprotection, but also to test several drug administration regimens to maximize the chance of detecting any therapeutic effect. However, GW405833 failed to provide neuroprotection in any of our experiments. These results challenge how far the results of earlier studies into CB2 mediated neuroprotection as measured at early time points may be extrapolated to later time points or to other models.

KEYWORDS:

Brain damage; CB(2) receptor; Cannabinoid; GW405833; Hypoxia-ischemia

PMID:
24721671
DOI:
10.1016/j.neulet.2014.03.077
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center