Celebration of the 10th Anniversary of Neural Regeneration Research

<正>Dear Readers,We are very excited to celebrate the 10th anniversary of Neural Regeneration Research(NRR).With this first issue of 2017,we would like to express our sincere thanks for your continued support and wish you a Happy New Year!We would also like to share with you a brief overview of the growth of the journal in the past 10 years.     

The complex contribution of the astrocyte scar

正It is tempting to assign positive or negative roles to components of neurotrauma pathology,in an effort to generate an ordered picture and design therapeutic strategies accordingly.However nature is seldom so obliging.This principle is elegantly illustrated in a recent publication from Anderson,Sofroniew and colleagues(Anderson et al.,2016)which describes use of a     

Effect of water restrictions on the physiological parameters,psychological behavior and brain c-Fos expression in rat

1 Introduction Exposure to hostile stressors causes a series of coor- dinated responses in the body, such as alterations of neu- roendocrine secretion, immune reaction and behavioral manifestation to maintain homeostasis stability and sur-vival of the organisms. Stressors are divided into two main categories: physical, or systemic, and psychological, or emotional / processive. Each stressor might activate a spe- cific central pathway to induce a special neuroendocrine response, even cause stre…     

Application of the concept of continuous dopaminergic stimulation for the management of Parkinson’s disease

Continuous dopaminergic stimulation（CDS）is a prominent therapeutic concept for the treatment of Parkinson＇s disease（PD）,which proposes that continuous brain dopamine-receptor stimulation,rather than intermittent doses of oral L-dopa,prevents or manages L-dopa-induced dyskinesias（LIDs）.In the normal situation,dopaminergic neurons in the substantia nigra pars compacta fire tonically to keep the dopamine receptor stimulation at a steady-state level.But when the dopaminergic pathway is impaired,the dopamine receptor stimulation becomes intermittent or pulsatile.This pulsatile stimulation causes a series of gene and protein changes in striatal neurons,leading to alterations in the firing patterns of basal ganglia neurons that result in LIDs.Studies in animal models and clinical trials of PD have shown that approaches providing CDS,currently including patches,extended-release formulations of L-dopa or dopamine agonists,continuous delivery of apomorphine and duodenal L-dopa infusion,are associated with a decreased risk of LIDs.In this review,we summarize both preclinical and clinical evidence for the five methods that may provide CDS in theory and compare the advantages and disadvantages of these methods.     

Small molecules to prevent the neurodegeneration caused by α-synuclein aggregation

正Parkinson's disease (PD) is a neurodegenerative disorder belonging to a group of human pathologies known as synucleinopathies,which includes multiple system atrophy or dementia with Lewy bodies (Spillantini et al.,1998).These diseases share a common neuropathological feature,the presence ofα-synuclein (α-Syn) deposits,although they differ in the cellular and anatomical compartment in whichα-Syn inclusions accumulate.PD affects more than 1% of people over 60 years of age,thus being the second most prevalent neurodegenerative disease in the world and the most common synucleinopathy.The loss of do-     

In vivo patch clamp recording technique in the study of neurophysiology

The patch clamp recording technique in vivois a blind patch clamp recording methods to record the current of the spinal or cereral neurons of anaesthesia (or awake) animals. This technique can be used to study the synaptic function and plasticity in central nervous system in vivoin order to understand the physiological properties of the ion channels from an integrated point of view. The advantage of this technique have already presented itself in the study of the synaptic transmission and nervous network. Nowadays, in vivo patch whole-cell recording technique in combination with other techniques is becoming a common method in the research fields.     

Clearing the corpses：regulatory mechanisms,novel tools,and therapeutic potential of harnessing microglial phagocytosis in the diseased brain

Apoptosis is a widespread phenomenon that occurs in the brain in both physiological and pathological conditions. Dead cells must be quickly removed to avoid the further toxic effects they exert in the pa-renchyma, a process executed by microglia, the brain professional phagocytes. Although phagocytosis is critical to maintain tissue homeostasis, it has long been either overlooked or indirectly assessed based on microglial morphology, expression of classical activation markers, or engulfment of artiifcial phagocytic targetsin vitro. Nevertheless, these indirect methods present several limitations and, thus, direct obser-vation and quantiifcation of microglial phagocytosis is still necessary to fully grasp its relevance in the diseased brain. To overcome these caveats and obtain a comprehensive, quantitative picture of microglial phagocytosis we have developed a novel set of parameters. hTese parameters have allowed us to identify the different strategies utilized by microglia to cope with apoptotic challenges induced by excitotoxicity or inlfammation. In contrast, we discovered that in mouse and human epilepsy microglia failed to ifnd and engulf apoptotic cells, resulting in accumulation of debris and inlfammation. Herein, we advocate that the effciency of microglial phagocytosis should be routinely tested in neurodegenerative and neuro-logical disorders, in order to determine the extent to which it contributes to apoptosis and inlfammation found in these conditions. Finally, our ifndings point towards enhancing microglial phagocytosis as a novel therapeutic strategy to control tissue damage and inlfammation, and accelerate recovery in brain diseases.     

New directions for the Academy

Thank you for the opportunity to serve as your president these past 2 years. As my tem comes to a close. I want to spend this time talking with you about our Academy, our specialty and our future.     

ⅩⅩⅣ European Stroke Conference

Time：May 12-15,2015Venue：Vienna,Austria Email：m.g.hennerici@eurostroke.eu Website：http：//www.eurostroke.eu/On behalf of the European Stroke Conference（ESC）Programme Committee,it is my pleasure to invite you all to theⅩⅩⅣESC in Vienna,Austria,where the Conference first met at the turn of the century in 2000.We invite all of you to contribute to our annual meeting and acknowledge your support through submission of proposals for teaching courses,mini and educational symposia,lectures as well as new topics.We also invite you to submit abstracts for oral and poster sessions on our homepage www.eurostroke.     

Short-chain fatty acids in the context of Parkinson’s disease

Research on neurodegenerative diseases such as Alzheimer’s disease,Parkinson′s disease(PD),Huntington’s disease or amyotrophic lateral sclerosis is becoming increasingly important in our society.Due to the ageing of the population,the prevalence of these diseases continue to rise worldwide,and causal cures are not yet available(Erkkinen et al.,2018).This Perspective focusses on PD,a movement disorder of the central nervous system with an estimated prevalence between 65 and 1250/100,000 in Europe,affecting about 1 percent of the population older than 60 years.The clinical symptoms include motor symptoms like bradykinesia,tremor or rigidity which are associated with loss of dopaminergic neurons in the substantia nigra and their innervating axonal fibers to the striatum.Additional non-motor symptoms may consist in depression,hyposmia,cognitive decline or constipation due to impaired motility of the gastrointestinal tract.     

Effect of six-month standardized tertiary rehabilitation program on the activities of dally living in stroke patients with hemiplegia

BACKGROUND: At present, there are many studies on the rehabilitation therapy of stroke patients with hemiplegia, but there is deficiency of corresponding standardized rehabilitation program. OBJECTIVE: To explore the effects of standardized tertiary rehabilitation on the activities of daily living in stroke patients with hemiplegia within 6 months after attack. DESIGN: A clinical observation. SETTING: Department of Rehabilitation Medicine, Huashan Hospital of Fudan University. PARTICIPANTS: Eighty-two outpatients and inpatients with acute stroke were selected from the Department of Neurology, Shanghai Huashan Hosptial from January 1999 to June 2003, including 49 males and 33 females, 40–80 years of age, with a mean age of (65±11) years old. Inclusive criteria: According to the diagnostic standards for cerebrovascular diseases set by Fourth National Academic Meeting for Cerebrovascular Disease in 1995, the patients were diagnosed as new attack of cerebral infarction or cerebral hemorrhage, and confirmed by CT or MRI to be initial patients; They should be accorded with the following conditions, including within 1 week after stabilization of life signs, Glasgow coma score > 8 points, 40–80 years of age, with disturbance of limb function. Informed consents were obtained from all the patients or their relatives. Exclusive criteria: Patients were excluded due to active liver disease, liver and kidney malfunction, congestive heart failure, malignant tumor, history of dementia, failure in respiratory function, tetraplegia; cerebral infarction or cerebral hemorrhage for more than 3 weeks; unable to be followed up due to in other cities and provinces; psychiatric history; deafness and muteness. According to the will of the patients or their relatives, the patients who accepted the standardized rehabilitation program were enrolled as the treatment group (n =42), and the others as the control group (n =40). Approval was obtained from the ethical committee of the hospital. METHODS: All the patients were given routine therapies of internal medicine after admission. According to the conditions of Brunnstom recovery 6-phase evaluation, the patients in the treatment group were trained with the pre-designed comprehensive standardized rehabilitation program for corresponding period. At early period (within about 1 month after attack), the patients received rehabilitative interventions in the Department of Emergency or Department of Neurology, once a day, 45 minutes for each time, 5 times a week; At middle period (about 1–3 months after attack), the patients received rehabilitative interventions in the rehabilitation ward or center, once to twice a day, 30–45 minutes for each time, 4–5 days a week; At late period (about 3–6 months after attack), the patients received rehabilitative intervention mainly assisted by rehabilitation physician in the community, relatives and volunteers, 3–4 times a week, and they were followed in the house or outpatient department once every two weeks. MAIN OUTCOME MEASURES: The patients were evaluated blindly by the same rehabilitation physician using scale of modified Barthel index at admission and 1, 3 and 6 months after attack respectively. RESULTS: Totally 82 patients with acute stroke were enrolled, and 3 cases in the treatment group missed, including 2 cases died at 1 month after admission, and 1 case refused the follow up 10 days later, all the others were involved in the analysis of results. The scores of modified Barthel index at corresponding time points after admission in the treatment group were all obviously higher than those in the control group (P < 0.01), and the score differences were also obviously higher than those in the control group (P < 0.01). The activities of daily living at admission and 1, 3 and 6 months after admission in the treatment group were 22.50%, 46.43%, 75.95% and 89.52% of that of normal people respectively, and those in the control group were 17.09%, 25.77%, 43.38% and 55.00% respectively. The activities of daily living at admission and 1, 3 and 6 months in the treatment group were 131.66%, 180.17%, 175.08% and 162.76% of those in the control group. As compared with at admission, the percentage of the score difference to the total score at the ends of the 1st, 3rd and 6th months were 23.93%, 53.45% and 67.02% in the treatment group, while 8.67%, 25.36% and 36.98% in the control group. CONCLUSION: Standardized tertiary rehabilitation can obviously promote the activities of daily living in stroke patients with hemiplegia.     

X X IV European Stroke Conference

On behalf of the European Stroke Conference （ESC） Programme Committee it is my pleasure to invite you all to the X X IV ESC in Vienna, Austria, where the Conference first met at the turn of the century in 2000. We invite all of you to contribute to our annual meeting and acknowledge your support through submission of proposals for teaching courses, mini and educational symposia, lectures as well as new topics.     

No phylogeny without ontogeny — a comparative and developmental search for the sources of sleep-like neural and behavioral rhythms

A comprehensive review is presented of reported aspects and putative mechanisms of sleep-like motility rhythms throughout the animal kingdom.It is proposed that ’rapid eye movement(REM)sleep’ be regarded as a special case of a distinct but much broader category of behavior,’rapid body movement(RBM)sleep’,defined by intrinsically-generated and apparently non-purposive movements.Such a classification completes a 2×2 matrix defined by the axes sleep versus waking and active versus quiet.Although ’paradoxical’ arousal of forebrain electrical activity is restricted to warm-blooded vertebrates,we urge that juvenile or even infantile stages of development be investigated in cold-blooded animals,in view of the many reports of REM-like spontaneous motility(RBMs)in a wide range of species during sleep.The neurophysiological bases for motorically active sleep at the brainstem level and for slow-wave sleep in the forebrain appear to be remarkably similar,and to be subserved in both cases by a primitive diffuse mode of neuronal organization.Thus,the spontaneous synchronous burst discharges which are characteristics of the sleeping brain can be readily simulated even by highly unstructured neural network models.Neuromotor discharges during active sleep appear to reflect a hierarchy of simple relaxation oscillation mechanisms,spanning a wide range of spike-dependent relaxation times,whereas the periodic alternation of active and quiet sleep states more likely results from the entrainment of intrinsic cellular rhythms and/or from activity-dependent homeostatic changes in network excitability.     

In the presence of danger：the extracellular matrix defensive response to central nervous system injury

Glial cells in the central nervous system （CNS） contribute to formation of the extracellular matrix, which provides adhesive sites, signaling molecules, and a diffusion barrier to enhance efficient on and axon potential propagation. In the normal adult CNS, the extracellular matrix （ECM） is relatively stable except in selected regions characterized by dynamic remodeling. However, after trauma such as a spinal cord injury or cortical contusion, the lesion epicenter becomes a focus of acute neuroinflammation. The activation of the surrounding glial cells leads to a dramatic change in the composition of the ECM at the edges of the lesion, creating a perilesion environment dominated by growth inhibitory molecules and restoration of the peripheral/ central nervous system border. An advantage of this response is to limit the invasion of damaging cells and diffusion of toxic molecules into the spared tissue regions, but this occurs at the cost of inhibiting migration of endogenous repair cells and preventing axonal regrowth. The following review was prepared by reading and discussing over 200 research articles in the field published in PubMed and selecting those with significant impact and/or controversial points. This article highlights structural and functional features of the normal adult CNS ECM and then focuses on the reactions of glial cells and changes in the perilesion border that occur following spinal cord or contusive brain injury. Current research strategies directed at modifying the inhibitory perilesion microenvironment without eliminating the protective functions of glial cell activation are discussed.     

Effects of dexmedetomidine and dexketoprofen on the conduction block of rat sciatic nerve

Dexmedetomidine is a selective α2-adrenoceptor agonist that is used because of its sedative,anxiolytic,and analgesic effects.Dexketoprofen,which is used as an analgesic,is a nonselective nonsteroidal anti-inflammatory drug (NSAID).The use of dexmedetomidine and dexketoprofen as adjuvants to local anesthetics for the peripheral nerve is gradually increasing.In this study,we aimed to investigate the effects of different doses of dexmedetomidine and dexketoprofen on conduction block of rat sciatic nerve.The isolated sciatic nerve from adult rats was transferred to a nerve chamber.The compound action potentials (CAPs) were recorded from stimulated nerve with electrophysiological methods.Dexmedetomidine (n = 8) and dexketoprofen (n = 8) were administered in the chamber with cumulative concentrations of 10–9 to 10–5 M,and the CAPs were recorded for 5 and 10 minutes.The CAP parameters were calculated.Both dexmedetomidine and dexketoprofen significantly depressed all CAP parameters in a dose-dependent manner compared with the control group,i.e.,the group in which rats did not receive treatment.CAP parameters showed there was no significant difference in nerve conduction inhibition between dexmedetomidine and dexketoprofen.Higher doses of dexmedetomidine suppressed the conduction in the fast-conducting fibers;however,dexketoprofen was found to suppress the conduction in the slow-conducting fibers in a time-dependent manner and suppress the conduction in the medium- and slow-conducting fibers in a dose-dependent manner.These findings suggest that dexmedetomidine and dexketoprofen exhibit better anesthetic effects on peripheral nerve through different ways of action.The experimental procedures were approved by the Necmettin Erbakan University on January 30,2013 (approval No.2013-024).     

Over-specialization versus synergy in neuroscience:professionals’integration is more than the sum of its parts

Health care systems in industrialized countries are built around acute health problems(Etzwiler,1997).This approach is successful when the goal is to improve or overcome pathologies that result in severe health issues or death.With the recent tremendous improvement of the treatments of life-threatening conditions,the clinical focus has moved from short term results to the overall expected quality of life and longterm outcomes.Unfortunately,the new objectives imply to consider a multitude of interacting processes and variables.In fact,a complex interplay of biological systems(nervous,immune,and endocrine)works together in an integrated and synergistic way to deal with a constantly evolving environment,determining our physical,behavioral,and psychological/subjective conditions.This interplay is the mechanism that allows us to adapt promptly and appropriately to circumstances,the key feature for successful living.     

A Context-Based Analgesia Model in Rats: Involvement of Prefrontal Cortex

Cognition and pain share common neural substrates and interact reciprocally: chronic pain compromises cognitive performance, whereas cognitive processes modulate pain perception. In the present study, we established a non-drug-dependent rat model of context-based analgesia,where two different contexts(dark and bright) were matched with a high(52°C) or low(48°C) temperature in the hot-plate test during training. Before and after training,we set the temperature to the high level in both contexts.Rats showed longer paw licking latencies in trials with the context originally matched to a low temperature than those to a high temperature, indicating successful establishment of a context-based analgesic effect in rats. This effect was blocked by intraperitoneal injection of naloxone(an opioid receptor antagonist) before the probe. The context-based analgesic effect also disappeared after optogenetic activation or inhibition of the bilateral infralimbic or prelimbic sub-region of the prefrontal cortex. In brief, we established a context-based, non-drug dependent, placebo-like analgesia model in the rat. This model provides a new and useful tool for investigating the cognitive modulation of pain.     

Saccharomyces cerevisiae in neuroscience:how unicellular organism helps to better understand prion protein?

The baker's yeast Saccharomyces(S.)cerevisiae is a single-celled eukaryotic model organism widely used in research on life sciences.Being a unicellular organism,S.cerevisiae has some evident limitations in application to neuroscience.However,yeast prions are extensively studied and they are known to share some hallmarks with mammalian prion protein or other amyloidogenic proteins found in the pathogenesis of Alzheimer's,Parkinson's,or Huntington's diseases.Therefore,the yeast S.cerevisiae has been widely used for basic research on aggregation properties of proteins in cellulo and on their propagation.Recently,a yeast-based study revealed that some regions of mammalian prion protein and amyloidβ1–42 are capable of induction and propagation of yeast prions.It is one of the examples showing that evolutionarily distant organisms share common mechanisms underlying the structural conversion of prion proteins making yeast cells a useful system for studying mammalian prion protein.S.cerevisiae has also been used to design novel screening systems for anti-prion compounds from chemical libraries.Yeastbased assays are cheap in maintenance and safe for the researcher,making them a very good choice to perform preliminary screening before further characterization in systems engaging mammalian cells infected with prions.In this review,not only classical red/white colony assay but also yeast-based screening assays developed during last year are discussed.Computational analysis and research carried out using yeast prions force us to expect that prions are widely present in nature.Indeed,the last few years brought us several examples indicating that the mammalian prion protein is no more peculiar protein–it seems that a better understanding of prion proteins nature-wide may aid us with the treatment of prion diseases and other amyloid-related medical conditions.     

Changes in the latencies of visual-evoked potentials in people undergoing tennis training——Dynamic comparison before and after 8 weeks training

BACKGROUND： Some previous studies have shown that exercise is an important factor that affects the latencies of visual-evoked potentials （VEPs）. OBJECTIVE： To investigate the effects of spending a period of time undergoing tennis training on the latencies of VEPs by comparing the latencies of VEPs before tennis training with those after 8 weeks of tennis training. DESIGN, TIME AND SETTING： The non-randomly concurrent controlled experiment was performed in the Department of Human Movement Sciences, Physical Education College, Shandong Normal University from April to June 2007. PARTICIPANTS： In total, 45 healthy volunteers from Shandong Normal University were selected as subjects, including 31 students majoring in physical education （11 males and 5 females participated in the tennis training plan for 8 weeks）, and 14 students from other subjects. Informed consent was obtained. According to whether they were majoring in physical education or not, and whether or not they took part in tennis training, the students were divided into 3 groups： a tennis group of physical education students （n = 16） a non-tennis group of physical education students （n =15） and a non-tennis group of non-physical education students （n = 14）. METHODS： The subjects in the tennis group took part in a regular tennis training plan of 2 hours a day and 3 days per week, for 8 weeks, while the subjects in two non-tennis groups were not in the tennis training plan The NDI-200 neural electricity tester （Shanghai Haishen Medical Electronic Instrument Co., Ltd.） was used to measure VEPs before and after the experiment in all three groups, and to compare the latencies of VEPs recorded before training with those recorded after training. MAIN OUTCOME MEASURES： Comparison of the changes in latencies of VEPs before and after 8 weeks of tennis training. RESULTS： All 45 subjects finished the test and datas from all were included in the statistical analysis. There were no significant differences among all the three group     

Ketogenic diet versus ketoacidosis: what determines the influence of ketone bodies on neurons?

Glucose is the main energy substrate for neurons, however, at certain conditions, e.g. in starvation, these cells could also use ketone bodies. This approach is used in clinical conditions as the ketogenic diet. The ketogenic diet is actually a biochemical model of fasting. It includes replacing carbohydrates by fats in daily meal. Synthesis of ketone bodies β-hydroxubutirate, acetoacetate and acetone begins once glycogen stores have depleted in the liver. The ketogenic diet can be used to treat clinical conditions, primarily epilepsy. The mechanism of neuroprotective action of ketogenic diet is not very clear. It is shown that ketone bodies influence neurons at three different levels, namely, metabolic, signaling and epigenetic levels. Ketone bodies are not always neuroprotective. Sometimes they can be toxic for the brain. Ketoacidosis which is a very dangerous complication of diabetes mellitus or alcoholism can be taken as an example. The exact mechanism of how neuroprotective properties of ketone bodies reverse to neurotoxic is yet to be established.