TRH analog YM-14673 improves outcome following traumatic brain and spinal cord injury in rats: dose-response studies.

YM-14673 is a thyrotropin-releasing hormone (TRH) analog that has a modification of the N-terminal (pyroglutamyl) moiety of the tripeptide. It is longer acting than TRH and has substantially greater potency with regard to central facilitatory activity. In the present studies, the effect of YM-14673 was examined in rats following standardized traumatic brain or spinal cord injury. Pentobarbital-anesthetized animals were subjected to fluid-percussion-induced brain trauma to the parietal cortex or impact trauma to the thoracic spinal cord. After injury animals were randomly assigned to treatment with i.v. YM-14673 at varying doses--0.1 mg/kg (low), 1.0 mg/kg (moderate), or 10 mg/kg (high)--or equal volume physiological saline. Treatment with YM-14673 improved chronic neurological recovery after trauma in both injury models; optimal beneficial effects were found at a dose of 1.0 mg/kg. These findings confirm previous observations that TRH or TRH analogs may improve outcome after traumatic brain and spinal cord injury and are consistent with the hypothesis that TRH analogs preserving the C-terminus are effective in CNS trauma.