Studies Of Effects Of Spinal Cord Injuries (SCI) On Micturition Function And 5-HT Mediated Micturition Recovery After SCI

Neural circuits for micturition are controlled by the peripheral sensory system,the spinal cord,and the brain:whereas the filling reflex is mainly mediated by the spinal cord,the emptying reflex is mediated by the brain.Spinal cord injuries(SCI)and injuries at the brain stem level often disrupt the supraspinal tract that control the micturition.When such supraspinal control is lost,the synergy between the bladder and the eternal urinary sphincter(EUS)is greatly affected,resulting in co-contraction and low void efficiency,which cause enormous suffering in SCI patients.In this study,we first established multiple SCI models that include T10 spinal cord transection,L3 and L5 spinal cord crush,and T10 spinal cord contusion.After verifying their anatomical characteristics,we studied their effects on the micturition.All of these models,except for L5 spinal cord crush that directly injured the motor neurons controlling EUS,severely compromised the voluntary emptying of the bladder.Animals with these SCI accumulated significantly more residue urine,and showed lower voiding efficiency.Next,using a recently developed high efficiency retrograde labeling technique,we specifically targeted neurons in the pontine micturition center(PMC)that send axons to the lumbosacral spinal cord.After specific ablation of PMC micturition related neurons,we identified a characteristic EUS-EMG dyssynergia,with a lower voiding efficiency.5-HT,a widely expressed neuronal transmitter,exists in the nerve terminals of in the brain,sympathetic,parasympathetic,and motor neurons in the spinal cord.Its receptors are also broadly expressed in the central nervous system(CNS)including the lumbosacral spinal cord.When combining the 5-HT1A/2A receptor agonists,the voiding volume and efficiency substantially increased after T10 spinal cord transection.Furthermore,one SSIR:Fluoxetine,helped improving the micturition functions after T10 spinal cord contusion.Because fluoxetine,along with other SSIRs,are clinically approved to treat the depression.our results therefore shed light onto the clinical treatment for micturition functional recovery after SCI.