Effect of thyrotropin-releasing hormone on the time course of neurologic recovery after spinal cord injury in the rat.
Spinal cord injuries in rats were experimentally produced by compressing the cord at the eleventh thoracic vertebral level for 60 minutes with stainless steel screws (2 mm in diameter and 2.8 mm in length). The main neurologic signs produced by cord compression were motor as well as sensory deficits and urinary incontinence. Rats with a neurologic score, based on both motor and sensory deficits, of 1 (complete paraplegia but responsive to tail pinching) 24 hours after injury were used to study the relative effect of subcutaneous treatment with TRH once or twice daily for 7 consecutive days on the time course of recovery after spinal cord injury and the dose-dependency of this effect. Once daily (5, 15, or 45 mg/kg/day) or twice daily (2.5, 7.5, or 22.5 mg/kg x 2/day) treatment with TRH starting 24 hours after injury improved the neurological signs and reduced the incidence of urinary incontinence, dose-dependently. The minimum effective doses for once and twice daily treatments were 45 mg/kg/day and 7.5 mg/kg x 2/day. These results indicate that the neurologic recovery-accelerating effect of TRH administered 24 hours after cord injury for 7 days is dose-dependent and that a twice daily dosage schedule tends to produce better improvement in the neurologic state than a once daily schedule dose.
Hashimoto
T
T
Research and Development Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Fukuda
N
N
D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D009046:Motor Neurons / Q000187:drug effects; D009420:Nervous System / Q000473:pathology; D009475:Neurons, Afferent / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors
D013973:Thyrotropin-Releasing Hormone