Effects of gabapentin on muscle spasticity and both induced as well as spontaneous autonomic dysreflexia after complete spinal cord injury

We recently reported that the neuropathic pain medication, gabapentin (GBP; Neurontin), significantly attenuated both noxious colorectal distension (CRD)-induced autonomic dysreflexia (AD) and tail pinch-induced spasticity compared to saline-treated cohorts 2–3 weeks after complete high thoracic (T4) spinal cord injury (SCI). Here we employed long-term blood pressure telemetry to test, firstly, the efficacy of daily versus acute GBP treatment in modulating AD and tail spasticity in response to noxious stimuli at 2 and 3 weeks post-injury. Secondly, we determined whether daily GBP alters baseline cardiovascular parameters, as well as spontaneous AD events detected using a novel algorithm based on blood pressure telemetry data. At both 14 and 21 days after SCI, irrespective of daily treatment, acute GBP given 1 h prior to stimulus significantly attenuated CRD-induced AD and pinch-evoked tail spasticity; conversely, acute saline had no such effects. Moreover, daily GBP did not alter 24 h mean arterial pressure (MAP) or heart rate (HR) values compared to saline treatment, nor did it reduce the incidence of spontaneous AD events compared to saline over the three week assessment period. Power spectral density (PSD) analysis of the MAP signals demonstrated relative power losses in mid frequency ranges (0.2–0.8 Hz) for all injured animals relative to low frequency MAP power (0.02–0.08 Hz). However, there was no significant difference between groups over time post-injury; hence, GBP had no effect on the persistent loss of MAP fluctuations in the mid frequency range after injury. In summary, the mechanism(s) by which acute GBP treatment mitigate aberrant somatosensory and cardiophysiological responses to noxious stimuli after SCI remain unclear. Nevertheless, with further refinements in defining the dynamics associated with AD events, such as eliminating requisite concomitant bradycardia, the objective repeatability of automatic detection of hypertensive crises provides a potentially useful tool for assessing autonomic function pre- and post-SCI, in conjunction with experimental pharmacotherapeutics for neuropathic pain, such as GBP

Stellar Cruise Control: Weakened Magnetic Braking Leads to Sustained Rapid Rotation of Old Stars

Despite a growing sample of precisely measured stellar rotation periods and ages, the strength of magnetic braking and the degree of departure from standard (Skumanich-like) spindown have remained persistent questions, particularly for stars more evolved than the Sun. Rotation periods can be measured for stars older than the Sun by leveraging asteroseismology, enabling models to be tested against a larger sample of old field stars. Because asteroseismic measurements of rotation do not depend on starspot modulation, they avoid potential biases introduced by the need for a stellar dynamo to drive starspot production. Using a neural network trained on a grid of stellar evolution models and a hierarchical model-fitting approach, we constrain the onset of weakened magnetic braking. We find that a sample of stars with asteroseismically-measured rotation periods and ages is consistent with models that depart from standard spindown prior to reaching the evolutionary stage of the Sun. We test our approach using neural networks trained on model grids produced by separate stellar evolution codes with differing physical assumptions and find that the choices of grid physics can influence the inferred properties of the braking law. We identify the normalized critical Rossby number ${\rm Ro}_{\rm crit}/{\rm Ro}_\odot = 0.91\pm0.03$ as the threshold for the departure from standard rotational evolution. This suggests that weakened magnetic braking poses challenges to gyrochronology for roughly half of the main sequence lifetime of sun-like stars.Comment: 26 pages, 10 figure

Noxious Colorectal Distention in Spinalized Rats Reduces Pseudorabies Virus Labeling of Sympathetic Neurons

The retrograde transsynaptic tracer pseudorabies virus (PRV) has been widely used as a marker for synaptic connectivity in the spinal cord. Notably, the PRV-152 construct expresses enhanced green fluorescent protein (EGFP). We recently reported a significant attenuation of PRV-152 labeling of the intermediolateral cell column (IML) and celiac ganglia after complete T4 spinal cord transection versus sham injury in rats at 96 h after PRV-152 inoculation of the left kidney. Here we found a significant increase in noxious colorectal distention (CRD)-evoked c-Fos expression in spinal cords of injured versus sham rats without PRV infection. In order to assess whether enhancing neuronal activity in spinalized rats might increase PRV-152 labeling, we subjected awake spinalized rats to 1.5 h of intermittent noxious CRD either: (1) just prior to inoculation, or (2) 96 h after inoculation (n = 3/group). Equal numbers of spinalized rats in both groups received PRV-152 inoculations without CRD (non-stimulated; n = 3/group). At 96 h post-inoculation fixed spinal cords and left celiac ganglionic tissues were assessed for the distribution and quantification of EGFP-labeled cells. The injured cohort that received CRD just prior to PRV injection showed a significant reduction in EGFP-labeled cells in both the IML and left celiac ganglion compared to non-stimulated injured rats. In contrast, the injured cohort that received CRD 96 h after PRV-152 inoculation showed no differences in EGFP-labeled cell numbers in the IML or celiac ganglia versus non-stimulated injured rats. Interestingly, microglia near c-Fos-positive cells after acute CRD appeared more reactive compared to non-stimulated spinalized rats, and activated microglial cells markedly reduce viral transduction and progression following PRV inoculation of the CNS. Hence our results imply that increased CRD-induced c-Fos expression in the injured paradigm, prior to but not after PRV injection, further attenuates PRV-152 uptake, perhaps through changes in neuronal activity and/or innate neuro-immune responses

Stellar Cruise Control: Weakened Magnetic Braking Leads to Sustained Rapid Rotation of Old Stars

Despite a growing sample of precisely measured stellar rotation periods and ages, the strength of magnetic braking and the degree of departure from standard (Skumanich-like) spin-down have remained persistent questions, particularly for stars more evolved than the Sun. Rotation periods can be measured for stars older than the Sun by leveraging asteroseismology, enabling models to be tested against a larger sample of old field stars. Because asteroseismic measurements of rotation do not depend on starspot modulation, they avoid potential biases introduced by the need for a stellar dynamo to drive starspot production. Using a neural network trained on a grid of stellar evolution models and a hierarchical model-fitting approach, we constrain the onset of weakened magnetic braking (WMB). We find that a sample of stars with asteroseismically measured rotation periods and ages is consistent with models that depart from standard spin-down prior to reaching the evolutionary stage of the Sun. We test our approach using neural networks trained on model grids produced by separate stellar evolution codes with differing physical assumptions and find that the choices of grid physics can influence the inferred properties of the braking law. We identify the normalized critical Rossby number Ro _crit /Ro _⊙ = 0.91 ± 0.03 as the threshold for the departure from standard rotational evolution. This suggests that WMB poses challenges to gyrochronology for roughly half of the main-sequence lifetime of Sun-like stars