Effect of injury severity on lower urinary tract function after experimental spinal cord injury.

Lower urinary tract dysfunction is a serious burden for patients following spinal cord injury. Patients are usually limited to treatment with urinary drainage catheters, which can lead to repeated urinary tract infections and lower quality of life. Most of the information previously obtained regarding lower urinary tract function after spinal cord injury has been in completely transected animals. After thoracic transection in the rat, plasticity of local lumbosacral spinal circuitry establishes a "reflex bladder," which results in partial recovery of micturition, albeit with reduced voiding efficiency. Since at least half of cord-injured patients exhibit neurologically incomplete injury, rat models of clinically relevant incomplete contusion injury have been developed. With respect to lower urinary tract function, recent anatomical and physiological studies have been performed after incomplete thoracic contusion injury. The results show greater recovery of lower urinary tract function that varies inversely with the severity of the initial trauma and is positively correlated with time after injury. Recovery, as measured by coordination of the bladder with the external urethral sphincter, occurs between 1 and 4 weeks after spinal cord injury. It is associated with normalization of: serotonin immunoreactivity and glutamate receptor subunit mRNA expression in the dorsolateral nucleus that innervates the external urethral sphincter muscle, the response to glutamatergic pharmacological probes administered at the lumbosacral spinal cord level, and c-Fos activation patterns in the lumbar spinal cord. Understanding the mechanisms involved in this recovery will provide a basis for enhancing lower urinary tract function in patients after incomplete spinal cord injury.

Effect of spinal cord injury severity on alterations of the H-reflex.

The monosynaptic motoneuron response to stimulation of Ia afferents is known to be altered by spinal cord injury (SCI). Although the Hoffman (H)-reflex is a tool that is often used to measure this reflex in patients, there has not been a systematic study investigating the effect of SCI severity and time on the H-reflex. We used a clinically relevant model of spinal cord contusion (Mild and Moderate) as well as complete surgical transection to measure the H-reflex at 1, 4 and 8 weeks after injury. The H-reflex was recorded from rat hindpaw plantar muscles in order to measure the baseline reflex amplitude and its response to increased stimulus frequency, i.e. rate depression. We correlated the reflex amplitude at each frequency to spared white matter at the injury epicenter, hindlimb function and serotonin immunoreactivity associated with retrogradely labeled plantar muscle motoneurons. The three injury groups displayed different behavioral deficits and amount of spared white matter at all three times tested. H-reflex rate depression was abnormal in all three injury groups at all three time points. At 8 weeks, transected animals displayed more H-reflex rate depression than those with a mild contusion. Baseline H-reflex amplitude was increased in both contusion groups at 4 weeks and showed a positive linear correlation with serotonin immunoreactivity. This baseline amplitude was not increased after transection. Furthermore, in the contusion group, there was a U-shaped relationship between behavioral scores and H-reflex rate depression, suggesting that an intermediate sensitivity of the motoneuronal pool to afferent input is associated with better recovery of hindlimb function.

Tumor necrosis factor-alpha inhibits physiologically identified dorsal motor nucleus neurons in vivo.

Our previous studies have shown that tumor necrosis factor-alpha (TNF-alpha) activates solitary nucleus neurons involved in vago-vagal reflex control of gastric motility. Here, we describe the dual role of TNF-alpha as also modulating neurons in the dorsal motor nucleus of the vagus (DMN) that respond to gastric distention. A large majority of physiologically identified DMN neurons are rapidly and completely inhibited by exposure to TNF-alpha, suggesting that TNF-alpha may induce gastric stasis by functioning as a hormone that modulates both portions of this reflex pathway during illness.