Effects of diazepam on glutamatergic synaptic transmission in the hippocampal CA1 area of rats with traumatic brain injury

The activity of the Schaffer collaterals of hippocampal CA3 neurons and hippocampal CA1 neurons has been shown to increase after fluid percussion injury. Diazepam can inhibit the hyperexcitability of rat hippocampal neurons after injury, but the mechanism by which it affects excitatory synaptic transmission remains poorly understood. Our results showed that diazepam treatment significantly increased the slope of input-output curves in rat neurons after fluid percussion injury. Diazepam significantly decreased the numbers of spikes evoked by super stimuli in the presence of 15 μmol/L bicuculline, indicating the existence of inhibitory pathways in the injured rat hippocampus. Diazepam effectively increased the paired-pulse facilitation ratio in the hippocampal CA1 region following fluid percussion injury, reduced miniature excitatory postsynaptic potentials, decreased action-potential-dependent glutamine release, and reversed spontaneous glutamine release. These data suggest that diazepam could decrease the fluid percussion injury-induced enhancement of excitatory synaptic transmission in the rat hippocampal CA1 area.     

Submandibular puncture of the facial vein: An original route for endovascular therapy of cavernous sinus dural fistulas

Introduction

Carotid cavernous sinus fistulas are a potentially severe pathology. Their basic standard treatment is an occlusion of the CCF performed by retrograde venous catheterization via the inferior petrous sinus. When the inferior petrous sinuses are occluded, other alternative venous routes are possible with various subsequent difficulties and risks. We report an original and safe method for endovascular treatment using submandibular puncture of the facial vein.

Clinical cases

We report 4 cases of patients with severe unilateral carotid cavernous sinus fistula associated with the occlusion of both inferior petrous sinuses. A submandibular surgical puncture of the ipsilateral inferior facial vein permitted the catheterization of the fistula. Complete occlusion of carotid cavernous sinus fistula was obtained by using a combination of microcoils and Onyx™.

Discussion

When inferior petrous sinuses are occluded, endovascular treatment of carotid cavernous sinus fistulas is more difficult. After reviewing the other treatment options reported in the literature and their respective advantages and adverse effects, we describe an original technique based on the surgical puncture of the ipsilateral facial vein. The occlusion of the fistula is then obtained by using a combination of microcoils and Onyx™.

Conclusion

When the inferior petrous sinuses are occluded, an endovascular treatment for a carotid cavernous sinus fistula can be performed using an original and secure method. This method relies on a simple surgical puncture of the facial vein in the submandibular region, which then permits a retrograde catheterization of the carotid cavernous sinus fistula with no significant risk.     

神经肌肉促进技术对脑卒中后偏瘫患者肢体骨质疏松的疗效及作用机制

目的：通过检测脑卒中后偏瘫患者的骨密度（ BMD ）及血清瘦素（ LP ）、碱性磷酸酶（ ALP ）、骨钙素（BGP）、白介素-6（IL-6）水平,观察神经肌肉促进技术（NFT）对其肢体骨质疏松的影响。方法将52例脑卒中偏瘫患者随机分为治疗组和对照组,对照组行常规治疗,治疗组在常规治疗基础上早期给予NFT治疗。采用双能X线吸收法检测两组入院第2天及治疗6个月后的BMD,采用ELISA法检测两组血清LP、ALP、BGP、IL-6水平,并进行比较。结果6个月后两组患肢BMD、对照组健肢与患肢BMD比较差异均有统计学意义（P均＜0．05）;两组血清LP、ALP、BGP、IL-6水平比较差异均有统计学意义（P＜0．05或＜0．01）。结论 NFT能影响脑卒中后偏瘫患者骨代谢指标,增加偏瘫肢体BMD;NFT对防治脑卒中后偏瘫患者的骨质疏松有效。     

Dynamical facilitation governs glassy dynamics in suspensions of colloidal ellipsoids

One of the greatest challenges in contemporary condensed matter physics is to ascertain whether the formation of glasses from liquids is fundamentally thermodynamic or dynamic in origin. Although the thermodynamic paradigm has dominated theoretical research for decades, the purely kinetic perspective of the dynamical facilitation (DF) theory has attained prominence in recent times. In particular, recent experiments and simulations have highlighted the importance of facilitation using simple model systems composed of spherical particles. However, an overwhelming majority of liquids possess anisotropy in particle shape and interactions, and it is therefore imperative to examine facilitation in complex glass formers. Here, we apply the DF theory to systems with orientational degrees of freedom as well as anisotropic attractive interactions. By analyzing data from experiments on colloidal ellipsoids, we show that facilitation plays a pivotal role in translational as well as orientational relaxation. Furthermore, we demonstrate that the introduction of attractive interactions leads to spatial decoupling of translational and rotational facilitation, which subsequently results in the decoupling of dynamical heterogeneities. Most strikingly, the DF theory can predict the existence of reentrant glass transitions based on the statistics of localized dynamical events, called excitations, whose duration is substantially smaller than the structural relaxation time. Our findings pave the way for systematically testing the DF approach in complex glass formers and also establish the significance of facilitation in governing structural relaxation in supercooled liquids.The transformation of liquids into glasses is as ubiquitous as it is enigmatic. From the formation of obsidian during volcanic eruptions (1) and fabrication of superstrong metallic glasses (2) to exotic forms of slow dynamics in crystals of colloidal dimers (3) and Janus particles (4), glass formation pervades nature, industry, and academia. A vast majority of molecular glass-forming materials exhibit anisotropy in shape and interparticle interactions, which often has a profound influence on their glassy dynamics. The rapidly expanding repertoire of chemists has made it possible to design colloidal particles of desired shape and interactions that can serve as realistic experimental analogs of these molecular liquids (5). By contrast, prominent theories like the Adam–Gibbs (6) theory, random first-order transition (RFOT) theory (7, 8), and the dynamical facilitation (DF) theory (9, 10) have been tested predominantly on spherical glass formers with isotropic interactions, which exhibit gross features of glassy dynamics, but fail to capture the nuances of vitrification in complex systems.The discovery of growing static (11–16) and dynamic (17–21) length scales appears to support the thermodynamic perspective of the Adam–Gibbs and RFOT theories. However, the growth in static length scales over the dynamical range accessible to numerical simulations is often minuscule and much smaller than the corresponding growth in dynamic length scales (21, 22). This renders any causal connection between growing static length scales and growing timescales doubtful (22). Moreover, recent simulations (23) and colloid experiments (24) have shown that growing dynamical correlations in the form of string-like cooperative motion emerge naturally within the purely kinetic approach of the DF theory. To compound matters further, facilitation is present even within the RFOT framework, albeit as a consequence of slow dynamics rather than a cause (25). Thus, although DF has been shown to exist (23, 24, 26–29), its relative importance as a mechanism of structural relaxation is still debated (30–32). The application of the DF approach to complex glass formers will therefore not only enhance our understanding of glass transitions in these systems, but also help ascertain the relevance of facilitation in governing structural relaxation.Here, we apply the DF theory to elucidate glass formation in suspensions of colloidal ellipsoids with repulsive as well as attractive interactions. The DF theory claims that structural relaxation in glass-forming liquids proceeds via a process known as dynamical facilitation, whereby localized mobile regions, termed excitations, mediate motion in neighboring regions in a manner that conserves mobility (9, 10). We first show that the notions of localized excitations and facilitated dynamics can be extended even to orientational relaxation. Next, we demonstrate that the spatial decoupling of dynamical heterogeneities (DHs) observed in colloid experiments stems from the spatial decoupling of rotational and translational facilitation. Most importantly, the DF theory can predict the existence of recently observed reentrant glass transitions (33) from the density dependence of the concentration of excitations. Our findings not only highlight the importance of facilitated dynamics in anisotropic glass formers but also reinforce the claim that, in the broader context of the glass transition, facilitation dominates structural relaxation.     

Chronic intermittent ethanol exposure during adolescence: Effects on social behavior and ethanol sensitivity in adulthood

This study assessed long-lasting consequences of repeated ethanol exposure during two different periods of adolescence on 1) baseline levels of social investigation, play fighting, and social preference and 2) sensitivity to the social consequences of acute ethanol challenge. Adult male and female Sprague-Dawley rats were tested 25 days after repeated exposure to ethanol (3.5 g/kg intragastrically [i.g.], every other day for a total of 11 exposures) in a modified social interaction test. Early-mid adolescent intermittent exposure (e-AIE) occurred between postnatal days (P) 25 and 45, whereas late adolescent intermittent exposure (l-AIE) was conducted between P45 and P65. Significant decreases in social investigation and social preference were evident in adult male rats, but not their female counterparts following e-AIE, whereas neither males nor females demonstrated these alterations following l-AIE. In contrast, both e-AIE and l-AIE produced alterations in sensitivity to acute ethanol challenge in males tested 25 days after adolescent exposure. Ethanol-induced facilitation of social investigation and play fighting, reminiscent of that normally seen during adolescence, was evident in adult males after e-AIE, whereas control males showed an age-typical inhibition of social behavior. Males after l-AIE were found to be insensitive to the socially suppressing effects of acute ethanol challenge, suggesting the development of chronic tolerance in these animals. In contrast, females showed little evidence for alterations in sensitivity to acute ethanol challenge following either early or late AIE. The results of the present study demonstrate a particular vulnerability of young adolescent males to long-lasting detrimental effects of repeated ethanol. Retention of adolescent-typical sensitivity to the socially facilitating effects of ethanol could potentially make ethanol especially appealing to these males, therefore promoting relatively high levels of ethanol intake later in life.     

Multivesicular liposomal bupivacaine at the sciatic nerve

Clinical translation of sustained release formulations for local anesthetics has been limited by adverse tissue reaction. Exparel™ (DepoFoam bupivacaine) is a new liposomal local anesthetic formulation whose biocompatibility near nerve tissue is not well characterized. Exparel™ injection caused sciatic nerve blockade in rats lasting 240 min compared to 120 min for 0.5% (w/v) bupivacaine HCl and 210 min for 1.31% (w/v) bupivacaine HCl (same bupivacaine content as Exparel™). On histologic sections four days after injection, median inflammation scores in the Exparel™ group (2.5 of 4) were slightly higher than in groups treated with bupivacaine solutions (score 2). Myotoxicity scores in the Exparel™ group (2.5 of 6) were similar to in the 0.5% (w/v) bupivacaine HCl group (3), but significantly less than in the 1.31% (w/v) bupivacaine HCl group (5). After two weeks, inflammation from Exparel™ (score 2 of 6) was greater than from 0.5% (w/v) bupivacaine HCl (1) and similar to that from 1.31% (w/v) bupivacaine HCl (1). Myotoxicity in all three groups was not statistically significantly different. No neurotoxicity was detected in any group. Tissue reaction to Exparel™ was similar to that of 0.5% (w/v) bupivacaine HCl. Surveillance for local tissue injury will be important during future clinical evaluation.     

Interactions among paired-pulse facilitation and post-tetanic and long-term potentiation in the mossy fiber-CA3 pathway in rat hippocampus

Long-term potentiation (LTP) observed at the synapses of mossy fiber-CA3(MF-CA3) pathway differs from that observed at the Schaffer collateral-CA1 pathway (SC-CA1), in being independent of N-methyl-D-aspartate (NMDA) receptors. The induction and expression mechanisms of MF-CA3 LTP remain to be determined. We have compared the occurrence and magnitude of LTP with that of two other indicators of presynaptic plasticity, post-tetanic potentiation (PTP) and paired-pulse facilitation in control brain slices from young rats and in slices treated with phorbol-12, 13-diacetate (PDAc), a protein kinase C activator. Paired-pulse facilitation is a potentiation of the second of two responses at intervals of tens of milliseconds and is due to a presynaptic calcium increase. Tetanic stimulation of mossy fibers induced LTP is area CA3 in only 64% of slices. In those slices that showed LTP, the size of the PIP was significantly greater than in those slices that did not, and the degree of correlation between LTP and PTP amplitude overall was r = 0.7. The degree of paired-pulse facilitation before tetanic stimulation was also positively correlated to the occurrence and magnitude of LTP and PTP after tetanic stimulation. The correlation coefficient between PTP and PPF was 0.749 for all slices studied, while that between LTP and PPF was 0.835 overall. Application of PDAc potentiated synaptic transmission and abolished paired-pulse facilitation (control ratio of second to first response, 2.1; after PDAc ratio 0.8) and LTP. PTP was absent at the control stimulus intensity in PDAc, but was apparent if the stimulus intensity was reduced to give a response of the same amplitude as before administration of PDAc. Stable LTP was also accompanied by a marked decrease in paired-pulse facilitation. These data suggest that MF-CA3 LTP, PTP and paired-pulse facilitation share common mechanisms and are all at least primarily of presynaptic origin. The occurrence of large paired-pulse facilitation or PTP is a predictor of a preparation which will show LTP. It is likely that presynaptic [Ca^2-], is an essential factor in LTP, PTP and paired-pulse facilitation, as well as the potentiation induced by application of PDAc, but the factors which determine whether or not [Ca^2-], rises following these various stimuli are not clear from the techniques used in these investigations. © 1996 Wiley-Liss, Inc.     

Advancing Pharmacological Treatments for Opioid Use Disorder (ADaPT-OUD): an Implementation Trial in Eight Veterans Health Administration Facilities

BackgroundIdentifying effective strategies to improve access to medication treatments for opioid use disorder (MOUD) is imperative. Within the Veterans Health Administration (VHA), provision of MOUD varies significantly, requiring development and testing of implementation strategies that target facilities with low provision of MOUD.ObjectiveDetermine the effectiveness of external facilitation in increasing the provision of MOUD among VHA facilities with low baseline provision of MOUD compared to matched controls.DesignPre-post, block randomized study designed to compare facility-level outcomes in a stratified sample of eligible facilities. Four blocks (two intervention facilities in each) were defined by median splits of both the ratio of patients with OUD receiving MOUD and number of patients with OUD not currently receiving MOUD (i.e., number of actionable patients). Intervention facilities participated in a 12-month implementation intervention.ParticipantsVHA facilities in the lowest quartile of MOUD provision (35 facilities), eight of which were randomly assigned to participate in the intervention (two per block) with twenty-seven serving as matched controls by block.InterventionExternal facilitation included assessment of local barriers/facilitators, formation of a local implementation team, a site visit for action planning and training/education, cross-facility quarterly calls, monthly coaching calls, and consultation.Main MeasuresPre- to post-change in the facility-level ratio of patients with an OUD diagnosis receiving MOUD compared to control facilities.Key ResultsIntervention facilities significantly increased the ratio of patients with OUD receiving MOUD from an average of 18% at baseline to 30% 1 year later, with an absolute difference of 12% (95% confidence interval [CI]: 6.6%, 17.0%). The difference in differences between intervention and control facilities was 3.0% (95% CI: − 0.2%. 6.7%). The impact of the intervention varied by block, with smaller, less complex facilities more likely to outperform matched controls.ConclusionsIntensive external facilitation improved the adoption of MOUD in most low-performing facilities and may enhance adoption beyond other interventions less tailored to individual facility contexts.