Treatment with the thyrotropin-releasing hormone analog CG3703 restores magnesium homeostasis following traumatic brain injury in rats.
Treatment with thyrotropin-releasing hormone (TRH) analogs following traumatic injury to the central nervous system (CNS) improves neurological outcome through mechanisms that remain unclear. Previous studies have shown that traumatic brain injury is associated with a profound decline in intracellular free magnesium (Mgf) and in total tissue magnesium (Mgt), the extent of Mgf decline being linearly correlated to the severity of injury and resultant neurological deficit. We have used 31P magnetic resonance spectroscopy and atomic absorption spectrophotometry, respectively, to measure cerebral Mgf concentration and Mgf content in rats following fluid percussion brain trauma and treatment with the TRH analog, CG3703. Treatment at 30 min postinjury with CG3703 significantly improved Mgf when compared to saline-treated controls. There were no significant changes in Mgt, Na+, K+ or water content following CG3703 treatment. Since a decline in intracellular free magnesium may affect cellular bioenergetic status, calcium flux, activity of excitatory amino acids, opiate receptors, and the release of eicosanoids, these results suggest that the beneficial effects of treatment with TRH analogs after CNS trauma may be mediated through magnesium-dependent mechanisms.
Vink
R
R
Department of Neurology, University of California, San Francisco.
McIntosh
T K
TK
Faden
A I
AI
D000818:Animals; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D008274:Magnesium / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013054:Spectrophotometry, Atomic / Q000379:methods; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology
C031926:montirelin; D013973:Thyrotropin-Releasing Hormone; D012964:Sodium; D008274:Magnesium; D011188:Potassium