Disruption of bladder function and sexual reflexes are major complications following spinal cord injury (SCI). We examined the use of telemetric monitoring of corpus spongiosum penis (CSP) pressures for assessment of micturition and erectile events following SCI in rats. Pressure catheters were implanted in the bulb of the CSP of seven male Long-Evans hooded rats, subjected to a standardized weight drop SCI (10 g × 12.5 mm) at T10. CSP pressures were analyzed for spontaneously occurring micturition and erectile events, and during ex copula reflex erection tests until 25 days after SCI. Urine volume was determined until 21 days after SCI. Results show initial loss of bladder function after SCI with gradual return of reflex micturition. When compared to baseline (BL), micturition pressure characteristics after SCI included prolonged duration, increased area under the curve (AUC), increased mean pressures, increased number of pressure peaks, and increased peak frequency. At 21 days after SCI, the urine volume per micturition was significantly increased. The number of full erectile events decreased significantly following SCI. Pressure wave analyses demonstrated increased AUC, increased maximum pressures, increased suprasystolic peak duration, increased AUC of the suprasystolic peaks, and increased maximum pressures of the suprasystolic peaks during recovery. The number of partial erectile events decreased significantly following SCI. Ex copula reflex erection testing demonstrated significantly decreased latency. The study demonstrates that telemetric monitoring of CSP pressures in conscious rats is a valuable and reliable method for assessing recovery of autonomic function following SCI.
Changes in sensory function including chronic pain and allodynia are common sequelae of spinal cord injury (SCI) in humans. The present study documents the extent and time course of mechanical allodynia and cold hyperalgesia after contusion SCI in the rat using stimulation with graded von Frey filaments (4.97–50.45 g force) and ice probes. Fore- and hind-paw withdrawal thresholds to plantar skin stimulation were determined in rats with a range of SCI severities (10-g weight dropped from 6.25, 12.5, or 25 mm using the MASCIS injury device); animals with 25-mm injuries most consistently showed decreased hind-paw withdrawal thresholds to touch and cold, which developed over several weeks after surgery. Stimulation of the torso with graded von Frey hairs was performed at specified locations on the back and sides from the neck to the haunch. Suprasegmental responses (orientation, vocalization, or escape) to mechanical stimulation of these sites were elicited infrequently in the laminectomy control rats and only during the first 3 weeks after surgery, whereas in 25-mm SCI rats, such responses were obtained for the entire 10 weeks of the study. These data suggest that rats with contusion SCI may exhibit sensory alterations relevant to human spinal cord injuries.
The proinflammatory cytokine TNFα contributes to cell death in central nervous system (CNS) disorders by altering synaptic neurotransmission. TNFα contributes to excitotoxicity by increasing GluA2-lacking AMPA receptor (AMPAR) trafficking to the neuronal plasma membrane. In vitro, increased AMPAR on the neuronal surface after TNFα exposure is associated with a rapid internalization of GABAA receptors (GABAARs), suggesting complex timing and dose dependency of the CNS’s response to TNFα. However, the effect of TNFα on GABAAR trafficking in vivo remains unclear. We assessed the effect of TNFα nanoinjection on rapid GABAAR changes in rats () using subcellular fractionation, quantitative western blotting, and confocal microscopy. GABAAR protein levels in membrane fractions of TNFα and vehicle-treated subjects were not significantly different by Western Blot, yet high-resolution quantitative confocal imaging revealed that TNFα induces GABAAR trafficking to synapses in a dose-dependent manner by 60 min. TNFα-mediated GABAAR trafficking represents a novel target for CNS excitotoxicity.
Objective: To use magnetic resonance imaging (MRI) to characterize secondary injury immediately after spinal cord injury (SCI), and to show the effect of hypertonic saline on MRI indices of swelling, edema, and hemorrhage within the cord. Design: A prospective, randomized, placebo-controlled study. Setting: Research laboratory. Subjects: Twelve adult Long-Evans female rats. Interventions: Rats underwent a unilateral 12.5 mm SCI at vertebral level C5. Animals were administered 0.9% NaCl (n = 6) or 5% NaCl (n = 6) at 1.4 mL/kg intravenously every hour starting 30 minutes after SCI. Immediately after SCI, rats were placed in a 4.7T Bruker MRI system and images were obtained continuously for 8 hours using a home-built transmitter/receiver 3 cm Helmholtz coil. Rats were killed 8 hours after SCI. Measurements and Main Results: Quantification of cord swelling and volumes of hypointense and hyperintense signal within the lesion were determined from MRI. At 36 minutes after SCI, significant swelling of the spinal cord at the lesion center and extending rostrally and caudally was demonstrated by MRI. Also, at this time point, a hypointense core was identified on T1, PD, and T2 weighted images. Over time this hypointense core reduced in size and in some animals was no longer visible by 8 hours after SCI, although histopathology demonstrated presence of red blood cells. A prominent ring of T2-weighted image hyperintensity, characteristic of edema, surrounded the hypointense core. At the lesion center, this rim of edema occupied the entire unilateral injured cord and in all animals extended to the contralateral side. Administration of HS resulted in increased serum [Na], attenuation of cord swelling, and decreased volume of hypointense core and edema at the last time points. Conclusions: We were able to use MRI to detect rapid and acute changes in the evolution of tissue pathophysiology, and show potentially beneficial effects of hypertonic saline in acute cervical SCI.
We developed a novel technique to simultaneously monitor micturitions and erections in rats by using pressure monitoring within the corpus spongiosum of the penis (CSP). We present data validating this technique and report pressure waveform characteristics of micturition and erectile events during four different behavioral contexts in 10 awake, freely-moving male rats. Telemetric pressure transducers were implanted in the bulb of the CSP. CSP pressure was monitored while the animals were simultaneously recorded on video for determination of presence and volume (n = 7) of micturitions and while the animals underwent behavioral tests for determination of erections. Observed micturitions and CSP pressure waveforms characteristic of micturitions occurred simultaneously (r = 0.98) at a frequency of 32 +/- 4 micturitions per 24 h and with a volume of 0.95 +/- 0.12 ml/urination. Micturition duration recorded by CSP pressure and volume determined by urine weight were highly correlated (r = 0.82). We found that 100% of visually confirmed erectile events occurred simultaneously with CSP pressure waveforms characteristic of erections during ex copula reflex erection tests. During noncontact erection and mating tests more erections were identified by telemetry than by observation alone. Erections during mating tests had a different appearance than those seen in other contexts; they were shorter in duration (P < 0.05) and typically were characterized by a single suprasystolic CSP pressure peak, highlighting the context-specificity of erections. Quality of recordings remained stable in three of four rats we followed for 8 wk. We demonstrate that telemetric recording of CSP pressure provides a quantitative and qualitative assessment of penile erections and micturition in freely behaving rats.
This study objective was to compare antibiotic use, clinical and bacteriological outcomes for selective treatment of only Gram-positive clinical cases versus blanket therapy. Cows with mild or moderate clinical mastitis (CM) from a California Central Valley dairy herd were assigned to either a) a positive-control treatment group (PC) or b) a laboratory-culture-based treatment group (CB). Quarter cases assigned to PC received immediate intramammary (IMM) treatment with ceftiofur (Spectramast LC; Zoetis Inc., New York, NY) and repeated once a day for a total of 3 d. Quarters assigned to CB underwent culture over a 24 h period at DairyExperts Laboratory (DairyExperts Inc., Tulare, CA). Only quarters showing Gram-positive growth were treated the next day with the same therapy as cases assigned to PC. Mixed Models were used with cow included as a random effect. A total of 473 quarter cases of clinical mastitis from 425 cows were enrolled into the study. Results are summarized on Table 1. The selective treatment of only CM cases from which Gram-positive bacteria was isolated resulted in about half reduction both in the number of cases treated and in the number of IMM tubes used. Furthermore, the withholding of antibiotic treatment did not have any deleterious effect on time for milk to return visibly normal, bacteriological cure, new infection risk, CM recurrence or removal from the herd.
Abstract Data-driven discovery in complex neurological disorders has potential to extract meaningful syndromic knowledge from large, heterogeneous data sets to enhance potential for precision medicine. Here we describe the application of topological data analysis (TDA) for data-driven discovery in preclinical traumatic brain injury (TBI) and spinal cord injury (SCI) data sets mined from the Visualized Syndromic Information and Outcomes for Neurotrauma-SCI (VISION-SCI) repository. Through direct visualization of inter-related histopathological, functional and health outcomes, TDA detected novel patterns across the syndromic network, uncovering interactions between SCI and co-occurring TBI, as well as detrimental drug effects in unpublished multicentre preclinical drug trial data in SCI. TDA also revealed that perioperative hypertension predicted long-term recovery better than any tested drug after thoracic SCI in rats. TDA-based data-driven discovery has great potential application for decision-support for basic research and clinical problems such as outcome assessment, neurocritical care, treatment planning and rapid, precision-diagnosis.
