Effect of 21-aminosteroid on extracellular energy-related metabolites and amino acids after compression injury of rat spinal cord.
We evaluated in a rat model of severe spinal cord compression the effect of the 21-aminosteroid tirilazad on extracellular levels of energy metabolites and amino acids, until 3 h after injury. The compound was given i.v. 30 min before injury (3 mg/kg) and hourly thereafter (1.5 mg/kg). The findings were compared with previously reported effects of methylprednisolone. Both treated and untreated rats with spinal cord compression showed, at 10 min after injury, a five- to sixfold elevation of extracellular lactate above the preinjury level. There was no significant difference for lactate, pyruvate or lactate/pyruvate ratio between the treated and untreated injured groups at any time point after trauma. Glutamate was significantly elevated both in treated and untreated injured rats for 20 min after trauma. The mean glutamate level was lower in animals treated with 21-aminosteroid. However, there was no statistically significant difference between the treated and untreated rats at any time after trauma. There was no statistically significant difference between the groups for aspartate, serine, glutamine, histidine, glycine, threonine, taurine, alanine and tyrosine. In conclusion our findings indicate that, in the injured spinal cord, methylprednisolone and the 21-aminosteroid have differences and similarities, regarding their effects on energy and amino acid metabolism. The lowering of the lactate and arginine levels early after trauma seen with methylprednisolone pretreatment was absent after 21-aminosteroid pretreatment. However, the mean extracellular level of glutamate was lower with both methylprednisolone and 21-aminosteroid after injury, although the difference was not statistically significant between treated and untreated rats.
Farooque
M
M
Laboratory of Neuropathology, University Hospital, Uppsala, Sweden. mohammad.farooque@patologi.uu.se
Hillered
L
L
Holtz
A
A
Olsson
Y
Y
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D004353:Drug Evaluation, Preclinical; D004734:Energy Metabolism / Q000187:drug effects*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011281:Pregnatrienes / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013117:Spinal Cord Compression / Q000188:drug therapy* / Q000378:metabolism
D000596:Amino Acids; D018696:Neuroprotective Agents; D011281:Pregnatrienes; C053355:tirilazad