Neuroprotective Effect And Its Mechanism Of Ligustrazine On Secondary Spinal Cord Injury In Rats

Spinal cord injury (SCI) is commonly encounted in clinical orthopaedics and neurosurgery. It is estimated that the incidence rate of SCI is every year 20~40/ million in mostly coutries. At present, SCI continues to have devastating effects on society. Despite decades of dedicated rese arch,efforts toward improving neurologic outcome have shown little progress. It is now fairly well agreed on that there are two separate components that combine to produce neurologic damage in acute SCI,the primary and secondary injuries. The actual mechanical disruption and cellular release of electrolytes,metabolites, and lysozymes from injured spinal cord cells. A secondary injury cascade follows,apparently actively mediated by cellular and molecular processes that work through complex mechanism.These secondary mediators include entities such as edema,inflammation,growth factors,ischemia,reperfusion,cacium flux,and superoxide radicals.This secondary injury cascade has been the basis for much of the recent research into improving neurologic outcome in acute SCI.The primary injury of acute SCI include the mechanical process of cell death by necrosis that results from overwhelming cellular damage and occurs without cellular control. In contrast ,apoptosis is a univeral and morphologically distinct from of physiologically active cell dearth.Apoptotic cell dearth from a "decision" by the cell based on information from its environment,intemal metabolism, developmental history,and its genome. As has been shown in various cancer applications,the ability to block or limit apoptotic cell dearth can prove beneficial to cell survival and longevity. The ability to regulate apoptotic cell dearth and its relationship to secondary injury is unknown,but could have important ramifications for improved neuronal survival afteracute spinal cord injury.Apoptosis, or programmed cell death, may play an important role in secondary spinal cord injury. Apoptosis a process of cell "suicide" in which the cell actively kills itself at a physiological or pathological condition occurring injured spinal cord. It can be triggered by a variety of mechanisms including glutamatergic excitotoxicity, free radical damage, cytokines, and inflammatory injury. Increase of acidophila, condensation of chromatin in the nucleus, nuclear shrink -age and/or DNA fragmentation apoptotic body can be found in apoptotic neurous,Bd-2 protein is in bcl-2 related family of proteins , which appears to be involved in opposing apoptosis and the relative levels of these proteins determine whether a cell dies or survives. The most common three sites of localization for bcl-2 protein are mitochondria, endoplasmic reticulum, and nuclear membranes. The mechanisms of bcl-2 protein protecting cells areopposing oxidative stress, limiting free radical generation, and suppressing the activation of Caspases. Overexpression of human bcl-2 by transgenic technique in rat neurons can improve ischemic injury of brain and spinal cord.Bcl-2 protein can cause the formation of dimmer with proapototic protein bax, result in the inactivation of bax, and suppress apoptosis. Immediate early genes(IEGs) have been thought it is the tache which contacts between the acute actively dependent circumstance and gene long-term expression. C-fos and r-jun gene of lEGs have lower-level expression in manifold cell and take part in cellular growth,differentiation,information transfer.lt has been found that may play an important role in secondary spinal cord injury.The optimal management of acute spinal cord injury contines to evolve.Current pharmacologic treatment involves the use of intravenous methylprednisolone with 8 hours of the injury.Results of several randomized clinical trials indicate that methylprednisolone has a real role in providing clinical improvement. The preclinical search for better pharmacologic treatments has centered on the inhibition of detrimental posttraumatic pathochmical events,such as generation of free radicals,mediators of the inflammatory respones, and local neurotransmitter toxicity.