Effects of gabapentin on mechanical allodynia and gait alterations.

<p>(A) Schedule of gabapentin (GBP) treatment after the induction of neuropathy with paclitaxel (PTX) and behavioral testing (Test). Animals were allocated to four groups: two groups received paclitaxel and two vehicle (VEH) injections. After the induction of neuropathy, one vehicle and one paclitaxel group were treated with daily gabapentin injections, whereas the other two groups received vehicle. (B) Paclitaxel induced mechanical allodynia was significantly improved after 8 days of gabapentin treatment as well as (C) the dynamic gait parameter duty cycle, whereas (D) the gait parameter hind paw print area was not affected by gabapentin treatment. * p<0.05; *** p<0.001 (Two-way ANOVA).</p

Dose-dense paclitaxel treatment induces a sensory polyneuropathy in mice.

<p>(A) Schedule of paclitaxel treatment and behavioral as well as electrophysiological testing. Animals received paclitaxel at a dose of 20 mg paclitaxel/kg BW three times per week over four weeks with a cumulative dose of 240 mg/kg BW. (B) Paclitaxel treated animals gained less weight than controls, but their weight quickly normalized after the last injection. (C) Motor coordination in the rotarod test was comparable in paclitaxel and vehicle injected animals. (D) Paclitaxel treated animals developed mechanical allodynia with a significantly reduced mechanical withdrawal threshold of the hind paws as well as a (E) predominantly axonal neuropathy with a diminished sensory nerve action potential amplitude (SNAP) of the caudal nerve. (F) Alterations of the caudal nerve SNAP showed a strong positive correlation with the mechanical withdrawal threshold (dashed line depicts the 95% prediction interval). *** p<0.001 compared to the control group at the same time point (One-way ANOVA).</p

Paclitaxel induced polyneuropathy can be detected with the Catwalk method.

<p>(A) A typical Catwalk run; the animal crosses from right to left. Paws are automatically detected and labeled by the program, in this example right hind paw (RH) and the left forepaw. Examples of gait parameters for the right hind paw are displayed at the bottom of the graph in respect to the step cycle. (B) Animals treated with paclitaxel develop distinct gait alterations compared to vehicle controls. The swing phase (squares, long dashed line) increases, while the stance phase (open triangles, dotted line) and the duty cycle (circles, solid line) decreases. Duty cycle expresses the stance phase as a percentage of the entire step cycle (stand + swing). (C) The print area of the hind paws is also significantly reduced in neuropathic animals. (D) The duty cycle of the hind paws shows a small correlation with the mechanical withdrawal threshold of the animals. Similar results are obtained for the correlation of the (E) hind paw stance phase duration with the caudal nerve SNAP. Solid lines in (D-E) signify linear regression lines, while medium dashed lines depict the 95% prediction interval. * p<0.05; *** p<0.001; both compared to the control group at the same time point (One-way ANOVA).</p

Microglia, Monocytes, and the Recurrence of Anxiety in Stress-Sensitized Mice.

To the Editor: We read with great interest the article by Weber et al. (1) in Biological Psychiatry describing the effects of microglia elimination and repopulation on stress sensitization induced by repeated social defeat (RSD). The article highlights brain-immune interactions and, in particular, the importance of stress-primed microglia for monocyte accumulation in the brain of RSD-sensitized mice following acute stress. The transcriptomic analysis of microglia 24 days after RSD could be very useful to other researchers, so the authors may wish to make this information accessible to the community by depositing it to an appropriate data repository

Data_Sheet_1_Pre-hospital Triage of Acute Ischemic Stroke Patients—Importance of Considering More Than Two Transport Options.docx

Background: Patients with acute ischemic stroke (AIS) and large vessel occlusion benefit from rapid access to mechanical thrombectomy in addition to intravenous thrombolysis. Prehospital triage algorithms to determine the optimal transport destination for AIS patients with unknown vessel status have so far only considered two alternatives: the nearest comprehensive (CSC) and the nearest primary stroke center (PSC).Objective: This study explores the importance of considering a larger number of PSCs during pre-hospital triage of AIS patients.Methods: Analysis was performed in random two-dimensional abstract geographic stroke care infrastructure environments and two models based on real-world geographic scenarios. Transport times to CSCs and PSCs were calculated to define sub-regions with specific triage properties. Possible transport destinations included the nearest CSC, the nearest PSC, and any of the remaining PSCs that are not closest to the scene, but transport to which would imply a shorter total time-to-CSC-via-PSC.Results: In abstract geographic environments, the median relative size of the sub-region where a triage decision is required ranged from 34 to 92%. The median relative size of the sub-region where more than two triage options need to be considered ranged from 0 to 56%. The achievable reduction in time-to-thrombectomy (“benefit”) exceeded the increase in time-to-thrombolysis (“harm”) by a factor of 2 in 30.5–37.0% of the sub-region where more than two triage options need to be considered. Results were confirmed in geographic environments based on real-world urban and rural stroke care infrastructures.Conclusion: Pre-hospital triage algorithms for AIS patients that only take into account the nearest CSC and the nearest PSC as transport destinations may be unable to identify the optimal transport destination for a significant proportion of patients.</p

Post-traumatic stress disorder and beyond: an overview of rodent stress models.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder of high prevalence and major socioeconomic impact. Patients suffering from PTSD typically present intrusion and avoidance symptoms and alterations in arousal, mood and cognition that last for more than 1 month. Animal models are an indispensable tool to investigate underlying pathophysiological pathways and, in particular, the complex interplay of neuroendocrine, genetic and environmental factors that may be responsible for PTSD induction. Since the 1960s, numerous stress paradigms in rodents have been developed, based largely on Seligman's seminal formulation of 'learned helplessness' in canines. Rodent stress models make use of physiological or psychological stressors such as foot shock, underwater trauma, social defeat, early life stress or predator-based stress. Apart from the brief exposure to an acute stressor, chronic stress models combining a succession of different stressors for a period of several weeks have also been developed. Chronic stress models in rats and mice may elicit characteristic PTSD-like symptoms alongside, more broadly, depressive-like behaviours. In this review, the major existing rodent models of PTSD are reviewed in terms of validity, advantages and limitations; moreover, significant results and implications for future research-such as the role of FKBP5, a mediator of the glucocorticoid stress response and promising target for therapeutic interventions-are discussed

Radiological features in pediatric versus adult patients with PRES.

1<p>Diffusion weighted imaging was performed in 80 patients (10 pediatric, 70 adults).</p>2<p>Contrast-enhanced imaging was performed in 81 patients (16 pediatric, 65 adults).</p>3<p>Follow-up imaging was performed in 64 patients (14 pediatric, 50 adults).</p><p>Radiological features in pediatric versus adult patients with PRES.</p

Description of pediatric versus adult patients with PRES.

<p>Exact RR-levels at initial PRES toxicity missing in 3 patients (1 pediatric, 2 adult).</p><p>Description of pediatric versus adult patients with PRES.</p

Post-traumatic stress disorder and beyond: an overview of rodent stress models.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder of high prevalence and major socioeconomic impact. Patients suffering from PTSD typically present intrusion and avoidance symptoms and alterations in arousal, mood and cognition that last for more than 1 month. Animal models are an indispensable tool to investigate underlying pathophysiological pathways and, in particular, the complex interplay of neuroendocrine, genetic and environmental factors that may be responsible for PTSD induction. Since the 1960s, numerous stress paradigms in rodents have been developed, based largely on Seligman's seminal formulation of 'learned helplessness' in canines. Rodent stress models make use of physiological or psychological stressors such as foot shock, underwater trauma, social defeat, early life stress or predator-based stress. Apart from the brief exposure to an acute stressor, chronic stress models combining a succession of different stressors for a period of several weeks have also been developed. Chronic stress models in rats and mice may elicit characteristic PTSD-like symptoms alongside, more broadly, depressive-like behaviours. In this review, the major existing rodent models of PTSD are reviewed in terms of validity, advantages and limitations; moreover, significant results and implications for future research-such as the role of FKBP5, a mediator of the glucocorticoid stress response and promising target for therapeutic interventions-are discussed

Data_Sheet_1_Assessing spatial learning and memory in mice: Classic radial maze versus a new animal-friendly automated radial maze allowing free access and not requiring food deprivation.PDF

The radial arm maze (RAM) is a common behavioral test to quantify spatial learning and memory in rodents. Prior attempts to refine the standard experimental setup have been insufficient. Previously, we demonstrated the feasibility of a fully automated, voluntary, and stress-free eight-arm RAM not requiring food or water deprivation. Here, we compared this newly developed refined RAM to a classic manual experimental setup using 24 female 10–12 weeks old C57BL/6J mice. We used a lipopolysaccharide (LPS)-induced model of systemic inflammation to examine long-term cognitive impairment for up to 13 weeks following LPS injection. Both mazes demonstrated robust spatial learning performance during the working memory paradigm. The refined RAM detected spatial learning and memory deficits among LPS-treated mice in the working memory paradigm, whereas the classic RAM detected spatial learning and memory deficits only in the combined working/reference memory paradigm. In addition, the refined RAM allowed for quantification of an animal’s overall exploratory behavior and day/night activity pattern. While our study highlights important aspects of refinement of the new setup, our comparison of methods suggests that both RAMs have their respective merits depending on experimental requirements.</p