Short Conduction Delays Cause Inhibition Rather than Excitation to Favor Synchrony in Hybrid Neuronal Networks of the Entorhinal Cortex

How stable synchrony in neuronal networks is sustained in the presence of conduction delays is an open question. The Dynamic Clamp was used to measure phase resetting curves (PRCs) for entorhinal cortical cells, and then to construct networks of two such neurons. PRCs were in general Type I (all advances or all delays) or weakly type II with a small region at early phases with the opposite type of resetting. We used previously developed theoretical methods based on PRCs under the assumption of pulsatile coupling to predict the delays that synchronize these hybrid circuits. For excitatory coupling, synchrony was predicted and observed only with no delay and for delays greater than half a network period that cause each neuron to receive an input late in its firing cycle and almost immediately fire an action potential. Synchronization for these long delays was surprisingly tight and robust to the noise and heterogeneity inherent in a biological system. In contrast to excitatory coupling, inhibitory coupling led to antiphase for no delay, very short delays and delays close to a network period, but to near-synchrony for a wide range of relatively short delays. PRC-based methods show that conduction delays can stabilize synchrony in several ways, including neutralizing a discontinuity introduced by strong inhibition, favoring synchrony in the case of noisy bistability, and avoiding an initial destabilizing region of a weakly type II PRC. PRCs can identify optimal conduction delays favoring synchronization at a given frequency, and also predict robustness to noise and heterogeneity

Gabapentin for the hemodynamic response to intubation: systematic review and meta-analysis

Purpose Endotracheal intubation is the gold standard for securing the airway before surgery. Nevertheless, this procedure can produce an activation of the sympathetic nervous system and result in a hemodynamic response which, in high-risk patients, may lead to cardiovascular instability and myocardial ischemia. The aim of this review was to evaluate whether gabapentin can attenuate this response and whether such an attenuation could translate into reduced myocardial ischemia and mortality. Source We searched MEDLINE®, EMBASE™, CINAHL, AMED, and unpublished clinical trial databases for randomized-controlled trials that compared gabapentin with control, fentanyl, clonidine, or beta blockers for attenuating the hemodynamic response to intubation. Primary outcomes were mortality, myocardial infarction, and myocardial ischemia. Secondary outcomes were hemodynamic changes following intubation. Principal findings We included 29 randomized trials with only two studies at low risk of bias. No data were provided for the primary outcomes and no studies included high-risk patients. The use of gabapentin resulted in attenuation in the rise in mean arterial blood pressure [mean difference (MD), −12 mmHg; 95% confidence interval (CI), −17 to −8] and heart rate (MD, −8 beats·min−1; 95% CI, −11 to −5) one minute after intubation. Gabapentin also reduced the risk of hypertension or tachycardia requiring treatment (risk ratio, 0.15; 95% CI, 0.05 to 0.48). Data were limited on adverse hemodynamic events such as bradycardia and hypotension. Conclusion It remains unknown whether gabapentin improves clinically relevant outcomes such as death and myocardial infarction since studies failed to report on these. Nevertheless, gabapentin attenuated increases in heart rate and blood pressure following intubation when compared with the control group. Even so, the studies included in this review were at potential risk of bias. Moreover, they did not include high-risk patients or report adverse hemodynamic outcomes. Future studies are required to address these limitations

GM-CSF: A Promising Target in Inflammation and Autoimmunity

The cytokine, granulocyte macrophage-colony stimulating factor (GM-CSF), was firstly identified as being able to induce in vitro the proliferation and differentiation of bone marrow progenitors into granulocytes and macrophages. Much preclinical data have indicated that GM-CSF has a wide range of functions across different tissues in its action on myeloid cells, and GM-CSF deletion/depletion approaches indicate its potential as an important therapeutic target in several inflammatory and autoimmune disorders, for example, rheumatoid arthritis. In this review, we discuss briefly the biology of GM-CSF, raise some current issues and questions pertaining to this biology, summarize the results from preclinical models of a range of inflammatory and autoimmune disorders and list the latest clinical trials evaluating GM-CSF blockade in such disorders