Kynurenate attenuates the accumulation of diacylglycerol and free fatty acids after experimental brain injury in the rat.
This study examined the effects of the administration of kynurenate, a non-specific excitatory amino acid (EAA) receptor subtype antagonist, on the regional accumulation of diacylglycerol (DG) and free fatty acids (FFAs) after lateral fluid percussion (FP) brain injury in the rat. After brain injury of moderate severity (2.0 atm), rats were treated with either kynurenate (200 mg/kg, i.v.) or saline at 5 min after injury. In the saline-treated brain-injured rats, levels of all individual DG-fatty acids (palmitic, stearic, oleic and arachidonic acids) and total DG-fatty acids were increased in the ipsilateral left cortex and hippocampus at 30 min and 60 min after injury. Kynurenate administration attenuated increases of individual and total DG-fatty acids in the ipsilateral cortex at 30 and 60 min and in the ipsilateral hippocampus at 30 min after FP brain injury. At 30 and 60 min after FP brain injury, increases in the levels of individual FFAs (palmitic, stearic, oleic and arachidonic acids) and of total FFAs were also observed in the ipsilateral cortex and hippocampus of the saline-treated injured rats. Kynurenate administration attenuated increases of all individual and total FFAs in the ipsilateral cortex and hippocampus either at 30 min alone or at both 30 min and 60 min after FP brain injury. In the contralateral cortex, levels of both DG-fatty acids and FFAs were not increased in the saline-treated injured rats and were also not affected by the administration of kynurenate. These results support the role of EAA receptor subtypes in the phospholipases-catalyzed formation of DG and FFAs in the ipsilateral cortex and hippocampus after lateral FP brain injury.
Dhillon
H S
HS
Department of Surgery, University of Kentucky Chandler Medical Center, Lexington, KY 40536, USA.
Prasad
R M
RM
D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D007736:Kynurenic Acid / Q000627:therapeutic use*; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004075:Diglycerides; D018691:Excitatory Amino Acid Antagonists; D005230:Fatty Acids, Nonesterified; D010743:Phospholipids; D007736:Kynurenic Acid