Functional disturbances in brain following injury: search for underlying mechanisms.
It was shown previously that local cerebral glucose utilization is less than 50% of normal in all cortical areas of rat brain 3 days following a focal freeze-lesion and that this effect of trauma is significantly diminished by dexamethasone (0.25 mg/Kg/day), and by indomethacin (7.5 mg/Kg single dose). To elucidate the mechanism of action of steroids and non-steroidal antiinflammatory drugs in traumatized brain, the effects of dexamethasone and indomethacin on arachidonic acid release, malondialdehyde production and prostaglandin synthesis in the lesion area were investigated. Five seconds after a freezing lesion arachidonic acid was significantly increased in the lesion area of untreated animals. Neither dexamethasone nor indomethacin had any effect on this release. The thiobarbituric acid reaction, as an estimate of malondialdehyde and non-enzymatic free radical lipoperoxide formation from unsaturated free fatty acids showed no change in the control and lesion areas of untreated and both dexamethasone and indomethacin treated groups. There was a marked increase in PGF2 alpha, PGE2, PGD2 in the lesion area of untreated animals. Indomethacin prevented the formation of prostaglandins by more than 90% while dexamethasone had no effect. These results suggest that some components of the arachidonic acid metabolism must be involved in functional disturbances resulting from trauma while steroid action is mediated in injured brain independently from the prostaglandin cascade.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D001929:Brain Edema / Q000209:etiology; D001930:Brain Injuries / Q000150:complications / Q000503:physiopathology*; D003907:Dexamethasone / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D008054:Lipid Peroxides; D011453:Prostaglandins; D016718:Arachidonic Acid; D003907:Dexamethasone; D005947:Glucose; D007213:Indomethacin