The Roles Of Brain-derived Neurotrophic Factor In Experimental Model Of Acute And Severe Compression-induced Cauda Equina Syndrome And Clinical Researches

Objective: To investigate the DDT&E [design, development, test and evaluation] of PLGA-BDNF biodegradable nanospheres as intrathecal injection for treating cauda equina syndrome and an experimental constriction injury of the lower lumbosacral central processes of the dorsal root ganglia resulting in the cauda equina syndrome (CES) in dogs and correlated clinical study of cauda equina syndrome.Methods: (1) Application of poly (lactide-co -glycolide)(PLGA) as a carrier and prepare PLGA-BDNF nanospheres using a double emulsion/solvent evaporation technique. (2) Etablishment of an experimental model of acute and severe multiple cauda equina constrictions (MCEC). (3) Investigation on the repair effect of intrathecal injection of BDNF-PLGA nanospheres on the sensory neurons of dorsal root ganglion of cauda equina syndrome induced by MCEC model. (4) To analyze possible expressing in the lower lumbosacral cord and development of pathophysiological mechanism in the compression -induced injury of cauda equina. (5) To determine the therapeutic effect after operation on within 48 hours of syndrome onset in patient with CES.Results: (1) Continuing observation for 4 week after removing cauda equina compression, the dogs of groupâ…¢showed a significant immunoreactivity of BDNF in neuronal population of the corresponding lumbar (L7) DRG and their neurological function and semiquantitative scoring had a significant improvement when compared with those of the groupsâ…¡andâ… . (2) Continuing observation for 4 week, pathological and immunohistochemical studies in groupâ…¡showed appreciable decrease in the number of neurons of corresponding lumbosacral cord and significant damage of spinal cord, especially the regions of white matter, when compared with the corresponding sham-operational group. BDNF is not express in large- and most medium-sized neurons in the lower lumbosacral cord of groupâ…¡, except the animals of cauda equina constrictions for 48 hours. (3) Surgery performed within 48 hours of syndrome onset had a significant improvement of neurological function.Conclusions: (1) We believe that the changes of BDNF expression in the lower lumbosacral cord play important roles in the pathophysiological mechanisms of CES because the BDNF/trkB receptor-mediated signaling pathway in the dorsal horn via an intact dorsal root is likely to be blocked by the acute and severe MCEC. (2) Intrathecal injection of BDNF-PLGA nanoparticles had obvious therapeutic effect in experimantal dogs of acute and severe CES. (3) Based on the evidence in this experimental study, the impaired extent of lower lumbosacral cord and neuronal degeneration on initial injury is the most important factor in predicting outcome following CES due to acute and severe MCEC. (4) Although the matter of the timing of surgery remains controversial, we recommend that surgery be performed within 48 hours of CES onset.