Effects of methylprednisolone on extracellular lactic acidosis and amino acids after severe compression injury of rat spinal cord.
We evaluated in rats with severe spinal cord compression at T8-9 the influence of methylprednisolone (MP) on lactic acidosis and extracellular amino acids, which may cause secondary, perifocal injuries of the cord. MP (30 mg/kg) was given intravenously 30 min before compression and hourly thereafter (15 mg/kg). Other rats with compression, given saline, served as controls. Samples from the extracellular fluid of one dorsal hom were collected by microdialysis and analyzed by HPLC. Microdialysis was performed for 1.5 h to establish basal levels. Samples were collected for 3 h after compression. MP-treated rats showed a reduction of dialysate lactic acid and arginine levels during the first 1-2 h after trauma. The mean dialysate levels of glutamate in MP-treated rats were lower than those of the controls, but the difference was not statistically significant. MP treatment did not influence dialysate levels of aspartate, glutamine, histidine, glycine, threonine, taurine, alanine, GABA, and tyrosine. Our study shows that MP has several effects, including reduced lactic acid formation, reduced levels of arginine (the substrate for nitric oxide production), and a trend toward decreased extracellular accumulation of the excitotoxic amino acid glutamate. We conclude that MP has the capacity to change the composition of the extracellular edema fluid after trauma to the spinal cord. These changes may counteract free radical formation and may be important mechanisms by which MP exerts its beneficial actions.
Farooque
M
M
Laboratory of Neuropathology, University Hospital, Uppsala, Sweden.
Hillered
L
L
Holtz
A
A
Olsson
Y
Y
D000140:Acidosis, Lactic / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D004734:Energy Metabolism; D005110:Extracellular Space / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013117:Spinal Cord Compression / Q000378:metabolism*
D000596:Amino Acids; D018698:Glutamic Acid; D001120:Arginine; D008775:Methylprednisolone