Changes in brain levels of N-acylethanolamines and 2-arachidonoylglycerol in focal cerebral ischemia in mice.
The N-acylethanolamines (NAEs) and 2-arachidonoylglycerol (2-AG) are bioactive lipids that can modulate inflammatory responses and protect neurons against glutamatergic excitotoxicity. We have used a model of focal cerebral ischemia in young adult mice to investigate the relationship between focal cerebral ischemia and endogenous NAEs. Over the first 24 h after induction of permanent middle cerebral artery occlusion, we observed a time-dependent increase in all the investigated NAEs, except for anandamide. Moreover, we found an accumulation of 2-AG at 4 h that returned to basal level 12 h after induction of ischemia. Accumulation of NAEs did not depend on regulation of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D or fatty acid amide hydrolase. Treatment with the fatty acid amide hydrolase inhibitor URB597 (cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester; 1 mg/kg; i.p.) 1.5 h before arterial occlusion decreased the infarct volume in our model system. Our results suggest that NAEs and 2-AG may be involved in regulation of neuroprotection during focal cerebral ischemia in mice.
Degn
Matilda
M
Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Denmark. matildadegn@gmail.com
Lambertsen
Kate L
KL
Petersen
Gitte
G
Meldgaard
Michael
M
Artmann
Andreas
A
Clausen
Bettina H
BH
Hansen
Steen H
SH
Finsen
Bente
B
Hansen
Harald S
HS
Lund
Trine M
TM
D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000235:genetics / Q000378:metabolism*; D001549:Benzamides / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D002545:Brain Ischemia / Q000150:complications / Q000201:enzymology / Q000473:pathology*; D002219:Carbamates / Q000494:pharmacology; D004195:Disease Models, Animal; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004983:Ethanolamines / Q000378:metabolism*; D005989:Glycerides / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D001095:Arachidonic Acids; D001549:Benzamides; D002219:Carbamates; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D005989:Glycerides; C022203:N-acylethanolamines; D012333:RNA, Messenger; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C094503:glyceryl 2-arachidonate