montirelin and Spinal-Cord-Injuries

Effects of thyrotropin-releasing hormone analog CG3703 on biochemical changes following impact spinal cord trauma were investigated by 31P magnetic resonance spectroscopy, atomic absorption spectrophotometry, high-pressure liquid chromatography and radioimmunoassay using parallel injury models in rabbits and rats. Treatment with CG3703 at 45 min after trauma in rabbits significantly attenuated decreases in intracellular pH and reversed increases in phosphodiester to phosphomonoester ratio, as shown by 31P magnetic resonance spectroscopy. The improved phosphodiester/phosphomonoester ratio was correlated with improved ATP status after treatment, although there was no improvement in aerobic bioenergetic capacity as reflected by phosphocreatine to inorganic phosphate ratios. In rats, treatment with CG3703 significantly reduced changes in tissue cations (Na+, K+, Mg2+) and water content following trauma, but did not significantly alter the accumulation of free fatty acids or thromboxane B2. Thus, the beneficial effects of treatment with thyrotropin-releasing hormone or thyrotropin-releasing hormone analogs on outcome following traumatic spinal cord injury may be due, in part, to actions relating to ion homeostasis.

Topics: Animals; Blood Pressure; Body Water; Dose-Response Relationship, Drug; Energy Metabolism; Hydrogen-Ion Concentration; Magnesium; Magnetic Resonance Spectroscopy; Phosphates; Phospholipids; Rabbits; Spinal Cord Injuries; Thyrotropin-Releasing Hormone

Effects of thyrotropin-releasing hormone (TRH) analogs were compared in rats to evaluate the structure-activity relationships of such compounds in the treatment of traumatic spinal cord injury. CG3703, a TRH analog having a modified amino-terminus, significantly improved motor recovery and somatosensory-evoked responses after trauma; in contrast, RX77368, which has a modified carboxy-terminus, was without effect, even at doses up to 10 mg/kg. These findings confirm and extend findings in cats, using other TRH analogs in a different model of spinal trauma. Together, data from rat and cat studies are consistent with the hypothesis that the integrity of the C-terminal amino acid may be critical for the beneficial effects of treatment with TRH and TRH analogs in experimental spinal injury, and suggest that a variety of other TRH analogs having substitutions of the pyroglutamyl or histidyl moieties of the tripeptide may also prove to be effective in the treatment of such injury.

Topics: Animals; Evoked Potentials, Somatosensory; Molecular Conformation; Pyrrolidonecarboxylic Acid; Rats; Spinal Cord Injuries; Thyrotropin-Releasing Hormone; Time Factors