We investigated levels and compositions of
N-acylethanolamines (NAEs) and their precursors, N-acyl
phosphatidylethanolamines (N-acyl PEs), in a rat
stroke model applying striatal microdialysis for
glutamate assay. Rats (n = 18) were treated with either intravenous saline (control),
NMDA receptor antagonist
MK801 (1 mg/kg), or
CB1 receptor antagonist
SR141716A (1 mg/kg) 30 min after permanent
middle cerebral artery occlusion (MCAO).
MK801 significantly attenuated the release of
glutamate in the infarcted striatum (79 +/- 22 micromol/L) as compared with controls (322 +/- 104 micromol/L). The administration of CB1 antagonist
SR141716A had no statistically significant effect on
glutamate release (340 +/- 89 micromol/L), but reduced
infarct volume at 5 h after MCAO significantly by approximately 40%, whereas
MK801 treatment resulted in a non-significant (18%) reduction of
infarct volume. In controls, striatal and cortical NAE concentrations were about 30-fold higher in the infarcted than in the non-infarcted hemisphere, whereas ipsilateral N-acyl
phosphatidylethanolamine (N-acyl PE) levels exceeded contralateral levels by only
a factor of two to three. Treatment with
MK801 or
SR141716A, or
glutamate release in the infarcted tissue, had no significant effect on these levels. NAE accumulation during
acute stroke may be due to increased synthesis as well as decreased degradation, possibly by inhibition of
fatty acid amide hydrolase (FAAH).