Spinal cord immunoreactive TRH is altered after local traumatic injury.

The effect of impaction-induced spinal trauma on the concentration of immunoreactive TRH (TRH-ir) in the spinal cord was studied. Samples were obtained from tissues proximal to, distal to, and at the site of injury at 30 min, 1 hr, 4 hr, and 6 weeks after impaction. After an initial 38% depletion of TRH-ir at the injury site at 30 min, concentrations were progressively elevated over time at all sites. These elevations reached statistical significance in the proximal and distal segments by 4 hr posttrauma. By 6 weeks, a rostral-caudal gradient of TRH-ir concentration was observed, indicating that axoplasmic transport was restricted. The gradient was characterized by a significant TRH-ir elevation proximal to, and a 60% depletion distal to, the injury. The short-term TRH-ir elevation measured indicates that the ability of exogenously administered TRH to reduce the incidence of posttraumatic functional deficit stems from a restoration of endogenous TRH action. The role of the raphe-spinal tract in the development of traumatic paralysis is considered.

Intraventricular 5,7-dihydroxytryptamine increases thyrotropin-releasing hormone content in regions of rat brain.

Rats received intraventricular (i.v.t.) injections of 5,7-dihydroxytryptamine (5,7-DHT) (100-600 micrograms). Some animals also received intraperitoneal injections of the 5-hydroxytryptamine uptake blocker fluoxetine (FX) (20 mg/kg) or the norepinephrine uptake blocker desmethylimipramine (DMI) (48 mg/kg) 30-90 min prior to i.v.t. 5,7-DHT. Rats were killed between 2 and 35 days following i.v.t. 5,7-DHT, brains were dissected, and regions were assayed for thyrotropin-releasing hormone (TRH) by radioimmunoassay. Dose-dependent increases in TRH content following i.v.t. 5,7-DHT were noted in the brainstem and hippocampus. DMI pretreatment blocked the increase in hippocampal TRH, but not in brainstem TRH. FX pretreatment was ineffective in blocking any increases in TRH content. These results suggest differential regulation of regional TRH content by interactions with specific neurotransmitter systems.

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.