The Initial Application Of A New Type Of Sacral Nerve Root Stimulator In Reconstructing The Function Of The Neurogenic Bladder After Spinal Cord Injury

With the rapid development of transportation and construction, the number of paraplegia worldwide due to spinal cord injuries has been rising annually. In all the patients with spinal cord injury, serious urinary retention, urinary tract infections, and bladder high-pressure causing bladder-ureteral reflux, even chronic renal failure, due to the bladder dysfunction, are the main cause of death in patients with paraplegia. In the past,most of the treatments are medication,intermittent catheterization,varieties of surgical treatments and so on.But these treatments' disadvantages are clear,such as ineffectiveness,long treatment cycle ,more complications and so on. So how to recover the controlling micturition function of spinal cord injured patients is always the worldwide medical problem。In 1976, Brindley,a British scholar, put forward sacral ventral nerve root electrical stimulation technology, which is based on the principle of different biological characteristics of detrusor and sphincte.When adoptting discontinuous impulse electrical stimulation to the sacral anterior nerve root, voiding can be caused because of the rising bladder pressure at the interval of the two stimuli.But this micturition way belongs to a kind of artificial micturition mode,and the stimulation parameters can't be appropriately adjusted, so sometimes the high bladder pressure may make the kidney damaged. Secondly,stimulating the sacral ventral root containing some nerve fibers that dominate the lower extremity can lead to the movement of the lower limb which is not convenient for the patients is to use。In view of this, in 1991, Rijkhoff put forward the anodal blocking technology, through which the parasympathetic nerve dominating the detrusor can be selectively excited. Thus that can change the micturition mode and eliminate the dithering of the limbs when undergoing electrical stimulating. This project focused on the anodal blocking technology and jointly developed a new sacral nerve root stimulator by Lilin university and Aalborg university of Denmark, expecting thrgis technology can change the original artificial mode of micturition after the stimulation of the sacral nerve root stimulator and the the dithering of the limbs when undergoing electrical stimulating.This will not only reconstruct the micturiton function of the bladder,but also provide inexpensive nerve root stimulator which is easy to use,leading to a reduction of the medical burden.It has an important practical significance for the prevention and control of the urinary infections,the improvement of the quality of life of patients with paraplegia and in prolonging the life.。ObjectiveExplore the application of the anode block electrical stimulation technology in the reconstruction of the neurogenic bladder function of the rabbits after spinal cord injury. Observe the changes of the basic physiological indexes of the experimental rabbits after a long-term electrical stimulation and carry out the inspection of the light microscopy, ultrastructure,and pathological morphology,evaluating the saftey of this electrical stimulation technology.Methods1.Subjects were 50 New Zealand rabbits, which were randomly assigned to the sham controls (n=10, sham-operated), and spinal cord injury groups (n=40, spinal cord clipping method to establish the complete spinal cord injury animal model)prior to surgery. The latter group, by urine flow mechanics screening (indicators include: residual volume, voiding urine, micturition efficiency, detrusor resting pressure, detrusor leak point pressure, detrusor maximum pressure, bladder compliance, and muscle electricity of urethral sphincter ) were randomly divided into neurogenic bladder model group and anode blocking electrical stimulation group。2.Sitimulate the sacral ventral nerve root with tripolar electrodes and long-pulse electrical stimulation after cut off the sacral posterior nerve root,to find out the stimulation parameters that can fully suppress the excitement of the motor nerve;after stimulating the sacral ventral nerve root for 4weeks with this stimulation parameters,explore the effect of the anode block electrical stimulation technology in the reconstruction of the rabbits' neurogenic bladder function after spinal cord injury,by comparing the urodynamic results between the controls and the SCI group。3.Stimulate the sacral nerve root of the rabbit continously in a short time with the electric stimulation, comparing changes of the basic phsiological indexes after stimulating for up to 120h.Observe the changes of the light microscope and ultrastructure,and the expression of the proteins,such as microtubules related proteins 2(Map-2), glial fibers acid protein(Gfap), cell apoptosis protein Bcl-2 and Bax, aspartate specificity half acid protease-3 protein (Caspase-3),in sacral nerve root by immunohistochemical stains and image analysis method. Count the positive cells.。Results1.50 animals: died during postoperative breeding(n=15); model establishment failure(n=3) ; sacral anterior nerve root injuried in the process of implanting the stimulating electrodes(n=5);in the process of electrical stimulation, intravesical pressure and urethral pressure showed weak response to electrical stimulation(n=1).24 New Zealand rabbits were excluded for these factors. Make statistical analysis in 9 of the control group, 9 of the model group and 8 of the electrical stimulation group.2.In the process of electrically stimulating the sacral anterior nerve root with tripolar electrodes and long-pulse electrical stimulation in the electrical stimulation group, we found that with the increase of stimulus current, the excitement of motor nerve were gradually suppressed. When the average stimulus pulse width was 300us,and the average stimulation current was 1.05mA, the urethral pressure dropped to zero and there will be a independent detrusor contraction. The dithering of the bilateral lower limbs can be reduced significantly.There is no significance in the maximum bladder pressure before and after injury and the voiding efficiency was close to the evel before injury. The urodynamic results after electrical stimulation for a long time indicate that,comparing with SCI group,the micturition volume, bladder capacity and voiding efficiency increased,while there was no significance in the maximum detrusor pressure, resting bladder pressure and bladder compliance,comparing with before SCI.3.After electrically stimulating for 120h,there is no significance in the changes of the breath, pulse and temperature comparing with before SCI. The ultrastructure of the nerve root demonstrated the myelin sheath was tightly packed, the sheath was thin with some of myelin loose and swelling,without demyelination phenomenon, a few mitochondrial slightly swollen,and some rough endoplasmic reticulum dilated.Organelles of the Schwann cells were not swelling.There was no neuronal atrophy,nucleolemma introcession,increased heterochromatin and so on.The results of the immunohistochemistry showed that,comparing with the control group,there was no significance in the change of the expression of Map-2, Gfap, Bax, Bcl-2, Caspase-3 in the electrical stimulation group.ConclusionThe new type of sacral nerve root stimultor can reconstruct the urinary bladder function of the rabbits after spinal cord injury effectively,with the physiological micturition model and remarkable decrease,even disappearance;in jitter in the process of electrical stimulation.Prolonged use sacral nerve root stimultor can reduce the residual urine volume, increase urine volume, bladder capacity,and voiding efficiency,reduce bladder detrusor leak point pressure and resting pressure,increase bladder compliance, improve symptoms of the urinary incontinence and urine reflux due to paraplegia,which can prolong the survival time after SCI of the rabbits.There was no obvious injury in the light microscopy and ultrastructural examination of the nerve root after electrical stimulation for a long time(120h),which was supported by immunohistochemistry.It is demonstrated that,with the pulse width of 300us and current stimulation of 1.05mA, sacral nerve roots showed good tolerance under this stimulus quantity without being injuried. Summary The new type of sacral nerve root stimulator base on anodal blocking technique can recover the bladder function,and electrical parameters is save and effectively.Innovation point1.Anodal blocking technology and sacral nerve root electrical stimulating technology are applied innovatively in treating with the neurogenic bladder after SCI,which not only makes the micturition model be close to physiology,but also inhibits the jitter of the bilateral lower extremities, making up the deficits of the traditional sacral nerve stimulator.2.Bladder urodynamic method are applied innovatively in assessing the improvement of the bladder function after long-term anode blocking electrical stimulation,exploring the saftey of the parameters of the anode blocking electrical stimulation using the immunohistochemistry, pathomorphology and so on,which will lay the foundation for the localization and clinical application of the sacral nerve root stimulator.