Treatment of experimental spinal trauma with thyrotropin-releasing hormone: central serotonergic and vascular mechanisms of action.
The sites and mechanisms by which thyrotropin-releasing hormone (TRH) may ameliorate the effects of spinal cord contusion were studied in the rabbit. We have examined the actions of an effective intravenous TRH infusion on the spinal content and utilization of the monoamine neurotransmitters (norepinephrine [NE], dopamine [DA], and serotonin [5-HT]) in both control and injured animals. The ability of TRH to penetrate the blood-brain barrier was determined by the measurement of spinal cord TRH immunoreactivity and the effect of TRH upon the development of traumatic edema was evaluated. TRH was found to enter the spinal cord to a large extent in approximately half the animals, but to a lesser degree in the remainder. This indicates the potential for a central site of action. In this regard, TRH induced a significant increase in the metabolism or utilization of 5-HT above the injury site. This effect was not observed in control animals. Finally, TRH was able to cancel the formation of edema at the injury site. These results are correlated with previously described mechanisms and are discussed in terms of the co-existence of TRH and 5-HT in raphe-spinal neurons descending from the medulla.
D000818:Animals; D001696:Biomechanical Phenomena; D001812:Blood-Brain Barrier; D002490:Central Nervous System / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D004298:Dopamine / Q000378:metabolism; D009420:Nervous System / Q000503:physiopathology; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D013973:Thyrotropin-Releasing Hormone / Q000493:pharmacokinetics / Q000627:therapeutic use*
D012701:Serotonin; D013973:Thyrotropin-Releasing Hormone; D004298:Dopamine; D009638:Norepinephrine