Plasticity of the central nervous system—a neurosurgeon's experience of cerebral compensation and decompensation

Summary Cerebral plasticity constitutes one of the most decisive factors in recovery and readaptation after cerebral lesions. In contrast to the considerable progress in current studies on normal neuronal plasticity including the idea of l'homme neuronal, the concept of plasticity postulated by Albrecht Bethe in 1929 received little attention. The author, as a neurosurgeon, has tried to describe cranial morphological plasticity, morphological and functional plasticity in infantile encephalopathies and especially in hemiatrophic lesions. It is supposed that a true morphological substrate exists due to compensatory hyperplasia of the uninvolved hemisphere.Modern neurosurgical techniques have demonstrated that the functional plastic capacity is much larger than has been supposed, even in the elderly. Some aspects of the mechanisms of compensation and decompensation of cortical and subcortical structures as well as of the central regulation systems are discussed. The full extent of the amazing recovery and functional reorganization is reached by plastic capacity, personal motivation, adequate training and sufficient time.The contribution ends with an exposition of a personal philosophy concerning psycho-somatic dualism, the body-mind problem, the future of the human brain and the ethical outlook, based on the progressive biological evolution of the basal neocortex and the immanent functional development (H. Spatz).In grateful memory of my paternal friends, the great German brain researchers Julius Hallervorden (1882–1965) and Hugo Spatz (1888–1969).     

Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4+ T Cell Responsiveness

Intermittent fasting and fasting mimetic diets ameliorate inflammation. Similarly, serum extracted from fasted healthy and asthmatic subjects’ blunt inflammation in vitro, implicating serum components in this immunomodulation. To identify the proteins orchestrating these effects, SOMAScan technology was employed to evaluate serum protein levels in healthy subjects following an overnight, 24-h fast and 3 h after refeeding. Partial least square discriminant analysis identified several serum proteins as potential candidates to confer feeding status immunomodulation. The characterization of recombinant IGFBP1 (elevated following 24 h of fasting) and PYY (elevated following refeeding) in primary human CD4⁺ T cells found that they blunted and induced immune activation, respectively. Furthermore, integrated univariate serum protein analysis compared to RNA-seq analysis from peripheral blood mononuclear cells identified the induction of IL1RL1 and MFGE8 levels in refeeding compared to the 24-h fasting in the same study. Subsequent quantitation of these candidate proteins in lean versus obese individuals identified an inverse regulation of serum levels in the fasted subjects compared to the obese subjects. In parallel, IL1RL1 and MFGE8 supplementation promoted increased CD4⁺ T responsiveness to T cell receptor activation. Together, these data show that caloric load-linked conditions evoke serological protein changes, which in turn confer biological effects on circulating CD4⁺ T cell immune responsiveness.     

雷公藤多甙片加益肾活血法治疗IgM相关性肾小球疾病

目的探讨IgM相关性肾小球疾病的治疗。方法53例患者分为雷公藤多甙片组(A组)和雷公藤多甙片＋中药益肾活血(B组)治疗,疗程2个月。结果两组治疗前后尿蛋白均下降（P＜0．05）,组间比较则B组降低更明显(P＜0．05)。尿红细胞均有减少,A组P＞0．05,B组P＜0．05;组间比较P＜0．05。结论雷公藤多甙片＋中药益肾活血法治疗IgM相关性肾小球疾病较单用雷公藤多甙片疗效显著提高。认为辨病辨证相结合组方用药,能够提高疗效。     

Impact of donor extracellular vesicle release on recipient cell “cross-dressing” following clinical liver and kidney transplantation

In several murine models of transplantation, the “cross-dressing” of recipient antigen presenting cells (APCs) with intact donor major histocompatibility complex (MHC) derived from allograft-released small extracellular vesicles (sEVs) has been recently described as a key mechanism in eliciting and sustaining alloimmune responses. Investigation of these processes in clinical organ transplantation has, however, been hampered by the lack of sensitivity of conventional instruments and assays. We have employed advanced imaging flow cytometry (iFCM) to explore the kinetics of allograft sEV release and the extent to which donor sEVs might induce cross-dressing following liver and kidney transplantation. We report for the first time that recipient APC cross-dressing can be transiently detected in the circulation shortly after liver, but not kidney, transplantation in association with the release of HLA-bearing allograft-derived sEVs. In liver transplant recipients the majority of circulating cells exhibiting donor HLA are indeed cross-dressed cells and not passenger leukocytes. In keeping with experimental animal data, the downstream functional consequences of the transfer of circulating sEVs harvested from human transplant recipients varies depending on the type of transplant and time posttransplant. sEVs released shortly after liver, but not kidney, transplantation exhibit immunoinhibitory effects that could influence liver allograft immunogenicity.     

Practice improves even the simplest movements

Summary Three subjects practiced accurate, fast elbow flexions of 54° to a 3° wide target. Movements of 36°, 54° and 72° were then tested. Comparison over the three distances showed that the normally monotonic relationship between movement distance and movement time is alterable by specific training. Subjects learn to go faster over the practiced distance by refining their neural commands to the muscles. The benefits of practice only partially transfer to other distances. We conclude that many of the relationships seen among movement variables in simple tasks are plastic in nature and affected by prior experience.     

Expression of activation markers on alveolar macrophages in allergic asthmatics after endobronchial or whole-lung allergen challenge

We examined the effect of endobronchial (EB) or whole-lung (WL) challenge with ragweed or Timothy grass extract on alveolar macrophage (AM) activation. Expression of 17 constitutive activation markers on AM was examined by flow cytometry. Late-phase bronchial obstruction was greater after WL challenge, while changes in bronchoalveolar lavage cytology (eosinophil accumulation) were greater after EB challenge. After EB challenge, levels of 10 of 17 markers (CD11a, CD11b, CD14, CD18, CD23, CD32, CD63, CD64, HLA-class I, and HLA-DR) were significantly increased (by 33-234%, P < 0.05). Six markers (CD16, CD29, CD33, CD35, CD44, CD71, and HLA-DQ) remained unchanged. Levels of seven markers following EB challenge (CD14, CD16, CD18, CD29, CD32, HLA-class I, and HLA DQ) correlated with airway sensitivity to methacholine. WL challenge only increased expression of HLA-class I. The different results obtained with the two challenge methods probably depend on higher local concentrations of allergen in the EB challenge. We suggest that activation of AM occurs following EB challenge with antigen in asthmatics.     

活化血小板表达在早期诊断和监测老年糖尿病肾病中的价值

目的 :探讨α颗粒膜蛋白 (CD62 P)和溶酶体膜蛋白 (CD63 )活化表达对老年糖尿病肾病早期诊断和病情监测的临床价值。方法 :采用流式细胞仪测定 196例老年 2型糖尿病患者 (其中单纯糖尿病 94例 ,糖尿病肾病 10 2例 )血浆CD62 P和CD63 水平 ,并与 40例健康人进行比较。同时观察糖尿病肾病血糖控制后CD62 P和CD63 的变化。结果 :单纯糖尿病组CD62 P和CD63 高于健康人组 (P <0 .0 0 1) ,糖尿病肾病组高于单纯糖尿病组 (P <0 .0 0 1) ,对糖尿病肾病患者进行血糖控制和抗凝治疗 6个月后 ,CD62 P、CD63 和 2 4h尿白蛋白排泄率 (UAER)水平下降 ,与对照组比较有显著性差异。结论 :CD62 P和CD63 对老年糖尿病肾病的早期诊断和病情监测有重要的临床价值     

补肾复方下调老年大鼠激活诱导的T细胞凋亡

目的　研究补肾复方延缓衰老的免疫学机制。方法　采用电镜、ＤＮＡ凝胶电泳及ＴＵＮＥＬ标记的流式细胞仪分析技术,对激活诱导的Ｔ细胞凋亡进行定性、定量分析。结果　老年大鼠对照组细胞凋亡的百分率为４７．０％,年龄大鼠组为２２．２％（Ｐ＜０．０１）;补肾组为３７．２％,与老年大鼠对照组相比有显著性差异（Ｐ＜０．０５）。结论　老年大鼠激活诱导Ｔ细胞凋亡的敏感性增高;补肾复方能降低激活诱导的老年大鼠Ｔ细胞凋亡,提示下调激活诱导Ｔ细胞凋亡可能是补肾延缓衰老的免疫学机制之一。     

FUNCTIONAL MAPPING OF THE HUMAN BRAIN DURING ACUPUNCTURE WITH MAGNETIC RESONANCE IMAGING SOMATOSENSORY CORTEX ACTIVATION

1NTRODUCTIONHegu(Ll4)isoneofthemosteffectiveandmostfrequentlyusedacupointsintraditionalChineseacupuncture.ItisindicatedfOrpaininmanypartsofthebody,butisparticularlyeffec-tiveforheadache,migraine,toothache,sorethroatandotherd1sordersoftheheadandface.Manyanimalexperimentsindicatethathighercentersinthenervoussystemareinvolvedinacupunctureanalgesia["2]butdirectevidenceforhumansubjectsisdifficulttoobtainuntilthere-centadventofpowerfu1andn0n-invasivemeth-odsforneuroimaginginthe9O's.Werecentlya…     

CD44: physiological expression of distinct isoforms as evidence for organ-specific metastasis formation

Continuous progress has been achieved during recent decades in the therapy of metastasizing malignancies by improving chemotherapeutic strategies and new approaches in radiation therapy. Genetic manipulation of tumor cells and of the tumor fighting immune system is hoped to add significant contributions to curative interventions in disseminated tumors. That we are still far from eradicating death by malignant growth is due ultimately to our limited understanding of the cascade of events resulting in metastasis formation, which until recently was believed to rely on multiple rounds of mutation and selection processes. This implies an individually specific history of each metastatic tumor, which would rule out uniform diagnostic and therapeutic concepts. When it was noted in a rat tumor model that the transfer of cDNA of a single gene, a CD44 variant isoform (CD44v) covering the exons v4–v7, sufficed to initiate metastasis formation of a locally growing tumor, hope was created that a metastogene may have been identified. Although the idea of CD44v expression as a unifying concept for tumor progression was not sustained, the discovery of CD44v-initiated metastatic spread allowed a conceptually new hypothesis on tumor progression as a consequence of the reactivation of genetic programs of ontogeny, stem cell differentiation, and/or lymphocyte activation. Since distinct CD44 isoforms play an important role in these processes, unraveling the functions of this family of molecules can indeed provide a cornerstone in the understanding of tumor progression. This article summarizes briefly the present knowledge on known functions of CD44 isoforms with particular focus on parallels between physiological programs and tumor progression.Abbreviations CD44s CD44 standard isoform - CD44v CD44 variant isoforms - HA Hyaluronate