Kinematic analysis of penile reflexes in a rat model of spinal cord injury.

The ex-copula penile dorsiflexion reflex (PDFR) is an established measure of sexual dysfunction in male rat models of spinal cord injury. Although the PDFR after complete spinal transection is well described, information regarding the more clinically relevant incomplete spinal contusion injury model is limited. This study examined, using two-dimensional (2D) kinematic analysis, the relationship between the PDFR and degree of white matter sparing (WMS). Male Wistar rats received a T9 contusion with varying degrees of impactor forces. Weekly kinematic recordings of the PDFR were made 3-8 weeks postinjury. Sexual reflex components examined included maximum angle of penile dorsiflexion, total penile event duration, and penile ascent speed. Post hoc comparison between animals grouped based upon injury severity (moderate-severe: 13.33%-17.15% WMS vs moderate: 20.85%-33.50% WMS) indicated PDFR effects. Specifically, the numbers of animals with more moderate contusions having data points above the median in both maximum angle of penile dorsiflexion and penile ascent speed were significantly lower than animals with more severe injuries. Total penile event duration was also affected but only at more chronic time points (6-8 weeks). Thus, 2D kinematic analysis of the PDFR allows for more consistent and quantifiable analysis of the subtle differences that can occur between injury severity groups in the rat contusion model.

Spinal cord stimulation for the restoration of bladder function after spinal cord injury.

Spinal cord injury (SCI) results in the inability to empty the bladder voluntarily, and neurogenic detrusor overactivity (NDO) and detrusor sphincter dyssynergia (DSD) negatively impact both the health and quality of life of persons with SCI. Current approaches to treat bladder dysfunction in persons with SCI, including self-catheterisation and anticholinergic medications, are inadequate, and novel approaches are required to restore continence with increased bladder capacity, as well as to provide predictable and efficient on-demand voiding. Improvements in bladder function following SCI have been documented using a number of different modalities of spinal cord stimulation (SCS) in both persons with SCI and animal models, including SCS alone or SCS with concomitant activity-based training. Improvements include increased volitional voiding, voided volumes, bladder capacity, and quality of life, as well as decreases in NDO and DSD. Further, SCS is a well-developed therapy for chronic pain, and existing Food And Drug Administration (FDA)-approved devices provide a clear pathway to sustainable commercial availability and impact. However, the effective stimulation parameters and the appropriate timing and location of stimulation for SCS-mediated restoration of bladder function require further study, and studies are needed to determine underlying mechanisms of action.

Telemetric monitoring of penile pressure during mating in rats after chronic spinal cord injury.

In men with a spinal cord injury (SCI), erectile function, ejaculation, and fertility are severely impaired. The present study utilized a telemetric pressure transducer implanted into the corpus cavernosum of the penis to examine sexual function during awake mating behavior in a rat contusion model with a range of Infinite Horizon Impactor forces distributed between 150 and 215 kdyn. The mating behavior paradigm included examination of the counts, average pressure, and average duration for mounts, intromissions, and ejaculations. Male Wistar rats were mated with receptive females in 30-min sessions preinjury (sexual acclimation) and once per week for 6 wk beginning after a 2-wk recovery period post-SCI. All SCI animals had significant deficits in sexual function in the parameters measured. These deficiencies were more prevalent in a subset having less than 20% white matter sparing, likely a reflection of the extent of bilateral spino-bulbo-spinal sexual circuitry disruption at the lesion epicenter. The resulting discoordination of the autonomic and somatic reflex control of erection and ejaculation recorded using telemetry devices in an awake, behaving animal model provides an effective means of gauging sexual function deficits after SCI and could have utility for quantifying recovery after a therapeutic intervention.

Activity-Based Training Alters Penile Reflex Responses in a Rat Model of Spinal Cord Injury.

INTRODUCTION: Multisystem functional gains have been reported in males with spinal cord injury (SCI) after undergoing activity-based training (ABT), including increases in scoring of sexual function and reports of improved erectile function. AIM: This study aims to examine the effect of daily 60-minute locomotor training and exercise in general on sexual function in a rat SCI contusion model. METHODS: Male Wistar rats received a T9 contusion SCI. Animals were randomized into 4 groups: a quadrupedal stepping group (SCI + QT), a forelimb-only exercise group (SCI + FT), a non-trained harnessed group (SCI + NT), and a home cage non-trained group (SCI + HC). The 2 non-trained groups were combined (SCI) post hoc. Daily training sessions were 60 minutes in duration for 8 weeks. Urine samples were collected during bi-weekly 24-hour metabolic cage behavioral testing. Latency, numbers of penile dorsiflexion, and glans cupping were recorded during bi-weekly penile dorsiflexion reflex (PDFR) testing. Terminal electromyography (EMG) recordings of the bulbospongiosus muscle (BSM) were recorded in response to stimulation of the dorsal nerve of the penis (DNP). OUTCOMES: ABT after SCI had a significant effect on PDFR, as well as BSM EMG latency and burst duration. RESULTS: SCI causes a significant decrease in the latency to onset of PDFR. After 8 weeks of ABT, SCI + QT animals had a significantly increased latency relative to the post-SCI baseline. BSM EMG response to DNP stimulation had a significantly decreased latency and increase in average and maximum amplitude in SCI + QT animals. SCI animals had a significantly longer burst duration than trained animals. Time between PDFR events, penile dorsiflexion, glans cupping, and urine testosterone were not affected by ABT. CLINICAL IMPLICATIONS: ABT has a positive influence on sexual function and provides a potential therapy to enhance the efficacy of current sexual dysfunction therapies in the male SCI population. STRENGTHS AND LIMITATIONS: Several significant small improvements in sexual function were found in a clinically relevant rat model of SCI using a readily available rehabilitative therapy. The limited findings could reflect insensitivity of the PDFR as a measure of erectile function. CONCLUSIONS: These results indicate that task-specific stepping and/or loading provide sensory input to the spinal cord impacting the neural circuitry responsible for sexual function. Steadman CJ, Hoey RF, Montgomery LR, et al. Activity-Based Training Alters Penile Reflex Responses in a Rat Model of Spinal Cord Injury. J Sex Med 2019; 16:1143-1154.

Activity-based Training on a Treadmill with Spinal Cord Injured Wistar Rats.

Spinal cord injury (SCI) results in lasting deficits that include both mobility and a multitude of autonomic-related dysfunctions. Locomotor training (LT) on a treadmill is widely used as a rehabilitation tool in the SCI population with many benefits and improvements to daily life. We utilize this method of activity-based task-specific training (ABT) in rodents after SCI to both elucidate the mechanisms behind such improvements and to enhance and improve upon existing clinical rehabilitation protocols. Our current goal is to determine the mechanisms underlying ABT-induced improvements in urinary, bowel, and sexual function in SCI rats after a moderate to severe level of contusion. After securing each individual animal in a custom-made adjustable vest, they are secured to a versatile body weight support mechanism, lowered to a modified three-lane treadmill and assisted in step-training for 58 minutes, once a day for 10 weeks. This setup allows for the training of both quadrupedal and forelimb-only animals, alongside two different non-trained groups. Quadrupedal-trained animals with body weight support are aided by a technician present to assist in stepping with proper hind limb placement as necessary, while forelimb-only trained animals are raised at the caudal end to ensure no hind limb contact with the treadmill and no weight-bearing. One non-trained SCI group of animals is placed in a harness and rests next to the treadmill, while the other control SCI group remains in its home cage in the training room nearby. This paradigm allows for the training of multiple SCI animals at once, thus making it more time-efficient in addition to ensuring that our pre-clinical animal model mimics the clinical representation as close as possible, particularly with respect to the body weight support with manual assistance.

Sex differences and effects of prenatal exposure to excess testosterone on ventral tegmental area dopamine neurons in adult sheep.

Prenatal testosterone (T) excess in sheep results in a wide array of reproductive neuroendocrine deficits and alterations in motivated behavior. The ventral tegmental area (VTA) plays a critical role in reward and motivated behaviors and is hypothesised to be targeted by prenatal T. Here we report a sex difference in the number VTA dopamine cells in the adult sheep, with higher numbers of tyrosine hydroxylase (TH)-immunoreactive (-ir) cells in males than females. Moreover, prenatal exposure to excess T during either gestational days 30-90 or 60-90 resulted in increased numbers of VTA TH-ir cells in adult ewes compared to control females. Stereological analysis confirmed significantly greater numbers of neurons in the VTA of males and prenatal T-treated ewes, which was primarily accounted for by greater numbers of TH-ir cells. In addition, immunoreactivity for TH in the cells was denser in males and prenatal T-treated females, suggesting that sex differences and prenatal exposure to excess T affects both numbers of cells expressing TH and the protein levels within dopamine cells. Sex differences were also noted in numbers of TH-ir cells in the substantia nigra, with more cells in males than females. However, prenatal exposure to excess T did not affect numbers of TH-ir cells in the substantia nigra, suggesting that this sex difference is organised independently of prenatal actions of T. Together, these results demonstrate sex differences in the sheep VTA dopamine system which are mimicked by prenatal treatment with excess T.