Effects Of Dynorphin And The Involvement Of Excitatory Amino Acid On Spinal Cord Injury

Spinal cord injury (Sd) includes primary injury and secondary injury subsequently induced by the primary injury. There is no effective treatment for SCI caused by primary injury at present. For this reason, secondary injury has become the major concern of many researchers. In recent years, dynorphin (Dyn), known as an important endogenous opiate peptide, is found to have a broad array of biological effects in the body. It had been recognized that Dyn, working as opiate peptide, is involved in the regulation of analgesia, cardiovascular activities, respiration, pituitary secretion and immunofunction. Recent studies have found that Dyn participates in secondary injury to the central nervous system, and that the injury effect of Dyn on the spinal cord may involve a non梠pium path other than opium receptor combination. Maybe EAA is related to the non梠pium path . The present study seeks to explore the Mechanism of SCI induced by Dyn and its relation to EAA in an attempt to provide experimental clues for clinical treatment of SCJ. The SCI model of the present study was established by injection of Dyn through subarachnoid intubat ion using modified Yalsh and Rudy methods. The changes of FAA were investigated with higherformance liquid chromatography. By using behavioral observation and such techniques as eiectrophysiology, histopathology, enzyme histochemistry and immunohistochemistry , quantitative studies were performed to observe changes in SCI induced by Dyn before and after intervention with Nethylspartic acid (NMDA) receptor antagonist of excitatory amina acid MK?01 and Kappa receptor antagonist norNI. The results are as follows: 1. The regional concentrations of FAA were elevated after Subarachnoid injection of Dyn. The elevation of EAA was related to the dosage other than the sorts of Dyn. The maximum of EAA concentration was acquired at the dosage of lOOnmol DynA(1-3). 2. Subarachnoid injection of Dyn produced impairing effect on the motor functions which were characterized as the decrease of Tarlov score and angulation increasing of Rivlin?s method .The impairment of motor function also emerged after intervention with MK?0l and nor桞NI at ld and 3d, but were released significantly at 7?4d . To compare with the group 4 Dyn, significant difference was found. There was no significantdifference between group MK--801 and nor--BNI.3. When determine the SEP and MEP, the pro1ongation of latencyand dec1ine of amplitude were observed after injection of Dyn. Simi1archanges occurred while injection of MK--80l and nor--BNI combined with Dynat 1d and 3d. The outcome of SEP and MEP was better than group Dynsignificantly at 7d and 14d.4. At 3d after the injection of Dyn, such damage of spina1 cordas 1oss of neuron, hemorrhage and necrosis of white matter and gray matter,increase of ACP activities were observed. Positive cell of GFAP,astrocytosis of gray matter and axona1 derangement were observed at week2. Such changes appeared in group MK--801 and nor--BNI at a lower degreewhen coIIlPared with group Dyn. There was no statistic difference betweengroup MK--801 and group nor--BNI.The resu1ts showed that subarachnoid injection of Dyn produced SCIin rats, accompanied with elevation of EAA in spinal cord. The effectsof Dyn were partly al1eviated when blocked either Kappa receptor or NMDAreceptor.In a word, The present study demonstrated that Dyn, working as a majorfactor of secondary SCI, wi11 resu1t in SCI at high concentration in spinalcord, and posed its injury effect through two paths: opium and non--opium;part of t...