Brain-wide activation involved in 15 mA transcranial alternating current stimulation in patients with first-episode major depressive disorder

Background Although 15 mA transcranial alternating current stimulation(tACS)has a therapeutic effect on depression,the activations of brain structures in humans accounting for this tACS configuration remain largely unknown.Aims To investigate which intracranial brain structures are engaged in the tACS at 77.5 Hz and 15 mA,delivered via the forehead and the mastoid electrodes in the human brain.Methods Actual human head models were built using the magnetic resonance imagings of eight outpatient volunteers with drug-naïve,first-episode major depressive disorder and then used to perform the electric field distributions with SimNIBS software.Results The electric field distributions of the sagittal,coronal and axial planes showed that the bilateral frontal lobes,bilateral temporal lobes,hippocampus,cingulate,hypothalamus,thalamus,amygdala,cerebellum and brainstem were visibly stimulated by the 15 mA tACS procedure.Conclusions Brain-wide activation,including the cortex,subcortical structures,cerebellum and brainstem,is involved in the 15 mA tACS intervention for first-episode major depressive disorder.Our results indicate that the simultaneous involvement of multiple brain regions is a possible mechanism for its effectiveness in reducing depressive symptoms.

Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.

PF4 and CXCL5 as potential diagnostic biomarkers and therapeutic targets for Parkinson’s disease complicated by ulcerative colitis

While accumulating evidence indicates a relationship between ulcerative colitis (UC) and Parkin-son’s disease (PD), the interactions between them have not been thoroughly examined. In this study we explored their association via genetic characterization and function-al enrichment. Assessment and validation were conducted in a novel dataset comprising whole blood RNA sequenc-ing (RNAseq) data and in three datasets retrieved from the Gene Expression Omnibus database (GSE107499, GSE75214, and GSE100054). Weighted gene co-expres-sion network analysis was used to determine the most rel-evant differentially expressed genes (DEGs) for the clin-ical features. Hub genes were identified using molecular complex detection (MCODE) application. In the training and validation datasets, we found two hub genes plate-let factor 4 (PF4) and C-X-C motif chemokine ligand 5 (CXCL5), which showed significant upregulation in all four datasets. The receiver operating characteristic curve indicated a diagnostic role for PF4 and CXCL5 in UC and PD. Therefore, PF4 and CXCL5 may provide key insights into the relationship between UC and PD.

Dysfunction of blood-brain barrier in cerebral amyloid angiopathy

Increasing evidence demonstrated that the blood-brain barrier(BBB)was involved in developing cerebral amyloid angiopathy(CAA).The BBB participates in the neurovascular coupling and regulates the transport of substances,which is closely related to neurodegenerative diseases.In CAA,the deposition of amyloid beta(Aβ)in arteries,capillaries,and arterioles of meninges and cerebral cortex results in the destruction of the BBB,chronic inflammatory response,chronic cerebral hypoperfusion,and dysfunction of the neurovascular unit,which eventually leads to neurodegeneration.At the same time,CAA is an age-related disease.Patients with CAA often have some risk factors for cerebrovascular diseases,such as hypertension and diabetes,which can further aggravate the damage to the BBB.Thus,it is of great significance to pay attention to the BBB in the pathogenesis and future intervention targets of CAA.Therefore,this manuscript reviewed the dysfunction of the BBB in CAA.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

Pathological significance of tRNA-derived small RNAs in neurological disorders

Non-coding RNAs(ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs(tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cleaved into a heterogeneous population of ncRNAs with lengths of 18–40 nucleotides, known as tRNA-derived small RNAs(tsRNAs). There are two main types of tsRNA, based on their length and the number of cleavage sites that they contain: tRNA-derived fragments and tRNA-derived stress-induced RNAs. These RNA species were first considered to be byproducts of tRNA random cleavage. However, mounting evidence has demonstrated their critical functional roles as regulatory factors in the pathophysiological processes of various diseases, including neurological diseases. However, the underlying mechanisms by which tsRNAs affect specific cellular processes are largely unknown. Therefore, this study comprehensively summarizes the following points:(1) The biogenetics of tsRNA, including their discovery, classification, formation, and the roles of key enzymes.(2) The main biological functions of tsRNA, including its miRNA-like roles in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress.(3) The potential mechanisms of pathophysiological changes in neurological diseases that are regulated by tsRNA, including neurodegeneration and neurotrauma.(4) The identification of the functional diversity of tsRNA may provide valuable information regarding the physiological and pathophysiological mechanisms of neurological disorders, thus providing a new reference for the clinical treatment of neurological diseases. Research into tsRNAs in neurological diseases also has the following challenges: potential function and mechanism studies, how to accurately quantify expression, and the exact relationship between tsRNA and miRNA. These challenges require future research efforts.

Neutrophil-derived interleukin-17A participates in neuroinflammation induced by traumatic brain injury

After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury(sub-acute phase), genome-wide transcriptomic data showed that interleukin 17 A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17 A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17 A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17 A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17 A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17 A may be a promising therapeutic target for traumatic brain injury.

Comparative transcriptomic analysis of rat versus mouse cerebral cortex after traumatic brain injury

The heterogeneity of traumatic brain injury(TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients.Targeting common processes across species may be an innovative strategy to combat debilitating TBI.In the present study, a cross-species transcriptome comparison was performed for the first time to determine the fundamental processes of secondary brain injury in Sprague-Dawley rat and C57/BL6 mouse models of TBI, caused by acute controlled cortical impact.The RNA sequencing data from the mouse model of TBI were downloaded from the Gene Expression Omnibus(ID: GSE79441) at the National Center for Biotechnology Information.For the rat data, peri-injury cerebral cortex samples were collected for transcriptomic analysis 24 hours after TBI.Differentially expressed gene-based functional analysis revealed that common features between the two species were mainly involved in the regulation and activation of the innate immune response, including complement cascades as well as Toll-like and nucleotide oligomerization domain-like receptor pathways.These findings were further corroborated by gene set enrichment analysis.Moreover, transcription factor analysis revealed that the families of signal transducers and activators of transcription(STAT), basic leucine zipper(BZIP), Rel homology domain(RHD), and interferon regulatory factor(IRF) transcription factors play vital regulatory roles in the pathophysiological processes of TBI, and are also largely associated with inflammation.These findings suggest that targeting the common innate immune response might be a promising therapeutic approach for TBI.The animal experimental procedures were approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No.201802001) on June 6, 2018.

Functional macrophages and gastrointestinal disorders

Macrophages(MΦ) differe ntiate from blood monocytes and participate in innate and adaptive immunity.Because of their abilities to recognize pathogens and activate bactericidal activities,MΦ are always discovered at the site of immune defense.MΦ in the intestine are unique,such that in the healthy intestine,they possess complex mechanisms to protect the gut from inflammation.In these complex mechanisms,they produce anti-inflammatory cytokines,such as interleukin-10 and transforming growth factor-β,and inhibit the inflammatory pathways mediated by Toll-like receptors.It has been demonstrated that resident MΦ play a crucial role in maintaining intestinal homeostasis,and they can be recognized by their unique markers.Nonetheless,in the inflamed intestine,the function of MΦ will change because of environmental variation,which may be one of the mechanisms of inflammatory bowel disease(IBD).We provide further explanation about these mechanisms in our review.In addition,we review recent discoveries that MΦ may be involved in the development of gastrointestinal tumors.We will highlight the possible therapeutic targets for the management of IBD and gastrointestinal tumors,and we also discuss why more details are needed to fully understand all other effects of intestinal MΦ.

Positive effects of music therapist's selected auditory stimulation on the autonomic nervous system of patients with disorder of consciousness: a randomized controlled trial

The current randomized controlled trial was performed at the China Rehabilitation Science Institute, China to test the hypothesis that musical auditory stimulation has positive effects on the autonomic nervous system of patients with disorder of consciousness.Although past studies have recommended that patients with disorder of consciousness listen to patient-preferred music, this practice is not universally accepted by researchers.Twenty patients with severe disorder of consciousness listened to either therapist-selected(n = 10, 6 males and 4 females;43.33 ± 18.76 years old) or patient-preferred(n = 10, 5 males and 5 females, 48.83 ± 18.79 years old) musical therapy, 30 minutes/day, 5 times/week for 6 weeks.The results showed no obvious differences in heart rate variability-related parameters including heart rate, standard deviation of normal-to-normal R-R intervals, and the root-mean-square of successive heartbeat interval differences of successive heartbeat intervals between the two groups of patients.However, percentage of differences exceeding 50 ms between adjacent normal number of intervals, low-frequency power/high-frequency power, high-frequency power norm, low-frequency power norm, and total power were higher in patients receiving therapist-selected music than in patients receiving their own preferred music.In contrast, this relationship was reversed for the high-frequency power and very-low-frequency band.These results suggest that compared with preferred musical stimulation, therapist-selected musical stimulation resulted in higher interactive activity of the autonomic nervous system.Therefore, therapist-selected musical stimulation should be used to arouse the autonomic nervous system of patients with disorder of consciousness.This study was approved by the Institutional Ethics Committee of China Rehabilitation Research Center, China(approval No.2018-022-1) on March 12, 2018 and registered with the Chinese Clinical Trial Registry(registration number Chi CTR1800017809) on August 15, 2018.

Genome-wide interrogation of transfer RNA-derived small RNAs in a mouse model of traumatic brain injury

Transfer RNA(t RNA)-derived small RNAs(ts RNAs) are a recently established family of regulatory small non-coding RNAs that modulate diverse biological processes. Growing evidence indicates that ts RNAs are involved in neurological disorders and play a role in the pathogenesis of neurodegenerative disease. However, whether ts RNAs are involved in traumatic brain injury-induced secondary injury remains poorly understood. In this study, a mouse controlled cortical impact model of traumatic brain injury was established, and integrated ts RNA and messenger RNA(m RNA) transcriptome sequencing were used. The results revealed that 103 ts RNAs were differentially expressed in the mouse model of traumatic brain injury at 72 hours, of which 56 ts RNAs were upregulated and 47 ts RNAs were downregulated. Based on micro RNA-like seed matching and Pearson correlation analysis, 57 differentially expressed ts RNA-m RNA interaction pairs were identified, including 29 ts RNAs and 26 m RNAs. Moreover, Gene Ontology annotation of target genes revealed that the significantly enriched terms were primarily associated with inflammation and synaptic function. Collectively, our findings suggest that ts RNAs may be associated with traumatic brain injury-induced secondary brain injury, and are thus a potential therapeutic target for traumatic brain injury. The study was approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No. 20190411) on April 11, 2019.

Motor neuron replacement therapy for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a motor neuron degenerative disease that is also known as Lou Gehrig’s disease in the United States,Charcot’s disease in France,and motor neuron disease in the UK.The loss of motor neurons causes muscle wasting,paralysis,and eventually death,which is commonly related to respiratory failure,within 3-5 years after onset of the disease.Although there are a limited number of drugs approved for amyotrophic lateral sclerosis,they have had little success at treating the associated symptoms,and they cannot reverse the course of motor neuron degeneration.Thus,there is still a lack of effective treatment for this debilitating neurodegenerative disorder.Stem cell therapy for amyotrophic lateral sclerosis is a very attractive strategy for both basic and clinical researchers,particularly as transplanted stem cells and stem cell-derived neural progenitor/precursor cells can protect endogenous motor neurons and directly replace the lost or dying motor neurons.Stem cell therapies may also be able to re-establish the motor control of voluntary muscles.Here,we review the recent progress in the use of neural stem cells and neural progenitor cells for the treatment of amyotrophic lateral sclerosis.We focus on MN progenitor cells derived from fetal central nervous system tissue,embryonic stem cells,and induced pluripotent stem cells.In our recent studies,we found that transplanted human induced pluripotent stem cell-derived motor neuron progenitors survive well,differentiate into motor neurons,and extend axons into the host white matter,not only in the rostrocaudal direction,but also along motor axon tracts towards the ventral roots in the immunodeficient rat spinal cord.Furthermore,the significant motor axonal extension after neural progenitor cell transplantation in amyotrophic lateral sclerosis models demonstrates that motor neuron replacement therapy could be a promising therapeutic strategy for amyotrophic lateral sclerosis,particularly as a variety of stem cell derivatives,including induced pluripotent stem cells,are being considered for clinical trials for various diseases.

Hierarchical platinum–iridium neural electrodes structured by femtosecond laser for superwicking interface and superior charge storage capacity

The interfacial performance of implanted neural electrodes is crucial for stimulation safety and the recording quality of neuronal activity.This paper proposes a novel surface architecture and optimization strategy for the platinum–iridium(Pt–Ir)electrode to optimize electrochemical performance and wettability.A series of surface micro/nano structures were fabricated on Pt–Ir electrodes with different combinations of four adjustable laser-processing parameters.Subsequently,the electrodes were characterized by scanning electron microscopy,energy-dispersive X-ray spectroscopy,cyclic voltammetry,electrochemical impedance spectroscopy,and wetting behavior.The results show that electrode performance strongly depends on the surface morphology.Increasing scanning overlap along with moderate pulse energy and the right number of pulses leads to enriched surface micro/nano structures and improved electrode performance.It raises the maximum charge storage capacity to 128.2 mC/cm^(2) and the interface capacitance of electrodes to 3.0×10^(4)μF/cm^(2) for the geometric area,compared with 4.6 mC/cm^(2) and 443.1μF/cm2,respectively,for the smooth Pt–Ir electrode.The corresponding optimal results for the optically measured area are 111.8 mC/cm^(2) and 2.6×10^(4)μF/cm^(2),which indicate the contribution of fner structures to the ablation profle.The hierarchical structures formed by the femtosecond laser dramatically enhanced the wettability of the electrode interface,giving it superwicking properties.A wicking speed of approximately 80 mm/s was reached.Our optimization strategy,leading to superior performance of the superwicking Pt–Ir interface,is promising for use in new neural electrodes.

Alzheimer's disease with sleep insufficiency:a cross-sectional study on correlations among clinical characteristics,orexin,its receptors,and the bloodbrain barrier

Previous studies have shown that reduced sleep duration,sleep fragmentation,and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling.At the same time,blood-brain barrier disruption is considered an early biomarker of Alzheimer's disease.However,currently no report has examined how changes in orexin signaling relate to changes in the blood-brain barrier of patients who have Alzheimer's disease with sleep insufficiency.This cross-sectional study included 50 patients with Alzheimer's disease who received treatment in 2019 at Beijing Tiantan Hospital.Patients were divided into two groups:those with insufficient sleep(sleep duration≤6 hours,n=19,age 61.58±8.54 years,10 men)and those with normal sleep durations(sleep duration>6 hours,n=31,age 63.19±10.09 years,18 men).Demographic variables were collected to evaluate cognitive function,neuropsychiatric symptoms,and activities of daily living.The levels of orexin,its receptor proteins,and several blood-brain barrier factors were measured in cerebrospinal fluid.Sleep insufficiency was associated with impaired overall cognitive function that spanned multiple cognitive domains.Furthermore,levels of orexin and its receptors were upregulated in the cerebrospinal fluid,and the blood–brain barrier was destroyed.Both these events precipitated each other and accelerated the progression of Alzheimer's disease.These findings describe the clinical characteristics and potential mechanism underlying Alzheimer's disease accompanied by sleep deprivation.Inhibiting the upregulation of elements within the orexin system or preventing the breakdown of the blood-brain barrier could thus be targets for treating Alzheimer's disease.

In vivo astrocyte-to-neuron reprogramming for central nervous system regeneration:a narrative review

The inability of damaged neurons to regenerate within the mature central nervous system(CNS)is a significant neuroscientific challenge.Astrocytes are an essential component of the CNS and participate in many physiological processes including blood-brain barrier formation,axon growth regulation,neuronal support,and higher cognitive functions such as memory.Recent reprogramming studies have confirmed that astrocytes in the mature CNS can be transformed into functional neurons.Building on in vitro work,many studies have demonstrated that astrocytes can be transformed into neurons in different disease models to replace damaged or lost cells.However,many findings in this field are controversial,as the source of new neurons has been questioned.This review summarizes progress in reprogramming astrocytes into neurons in vivo in animal models of spinal cord injury,brain injury,Huntington’s disease,Parkinson’s disease,Alzheimer’s disease,and other neurodegenerative conditions.

Association between brain N-acetylaspartate levels and sensory and motor dysfunction in patients who have spinal cord injury with spasticity:an observational case-control study

Spinal cord injury is a severe and devastating disease,and spasticity is a common and severe complication that is notoriously refractory to treatment.However,the pathophysiological mechanisms underlying spasticity and its development remain largely unknown.The goal of the present study was to find differences,if any,in metabolites of the left precentral gyrus and basal ganglia of patients who have spinal cord injury with or without spasticity,and to explore the relationship between the brain metabolite concentrations and clinical status.Thirty-six participants were recruited for magnetic resonance spectroscopic examination:23 with spinal cord injury(12 with spasticity and 11 without spasticity)and 13 healthy controls.We acquired localized proton spectra from the precentral gyrus and basal ganglia via 10 mm^(3) voxels.Notably,univariate linear regression analysis demonstrated that the lower that the N-acetylaspartate concentration(a marker for neuronal loss)was in the precentral gyrus of the patients,the lower their ASIA(American Spinal Injury Association)light-touch scores,pinprick scores,and motor scores.Additionally,longer durations of injury were associated with higher N-acetylaspartate levels in the precentral gyrus.Compared with the healthy participants and patients without spasticity,N-acetylaspartate levels in the patients with spasticity were significantly lower in both the precentral gyrus and basal ganglia.Lower N-acetylaspartate levels also correlated with greater sensory and motor dysfunction in the patients who had spinal cord injury with spasticity.

Latest progress in the research of protein kinase C(PKC)isoform-specific signaling and PKC-modulated autophagy in ischemic stroke

Ischemic stroke is a major cause of morbidity and mortality,and currently there is no effective treatment.The family of protein kinase C(PKCs)could phosphorylate serine or threonine residues of its substrate proteins and play a key role in the ischemia/reperfusion injury.Autophagy is essential for maintaining cell homeostasis under physiological condition and acts as a double-edged sword in the process of ischemic neuronal death.In this article,we reviewed the PKCs isoform-specific signaling pathways and PKC-modulated autophagy in ischemic stroke.

Moderate alcohol preconditioning activates BKCa channels to protect brain damage-induced by cerebral ischemia and reperfusion

OBJCETIVE Epidemiologic studies have demonstrated that consumption of moderate amounts of red wine is associated with significant reductions in incidences of cardiovascular and cerebrovascular diseases,which may be related to alcohol in red wine.Our previous study demonstrated that ethanol ingestion 24 h prior to induction of cerebral ischemic/reperfusion(I/R)reduced delayed neuronal death(DND).Our most recent results supported a role for big Ca2+-sensitive K+channel(BKCa channel)activation in the neuroprotective effects of ethanol preconditioning(Et OH-PC)in global cerebral I/R.Therefore,we hypothesis that moderate Et OH-PC activates BKCa channel to protect brain damage induced by focal cerebral I/R.This project will utilize focal cerebral I/R animal model to explore the function of BKCa channel in Et OH-PC protection in vivo levels by means of pharmacological intervention such as BKCa channel opene(rNS11021,NS)and blocke(rpaxilline,PX).The results will provide theoretical evidence for neuroprotective effect of moderate alcohol preconditioning against ischemic stroke,and the conclusion will also bring to a concept that extrinsic moderate ethanol preconditioning may activate intrinsic protective mechanism in the brain.METHODS The SD rat were randomly divided into the following six groups(n=10):sham,I/R,Et OH-PC+I/R,NS11021-PC+I/R,paxilline+Et OH-PC+I/R,Paxilline+NS11021-PC+I/R.Both Et OH-PC and NS11021-PC(0.1mg·kg-1;ip)were induced 24 h before I/R.The volume of 95%ethanol to be instilled(inμL)was calculated as follows:〔body weight(g)×0.6〕+0.3.This volume of ethanol was mixed in 0.3 m L of sterile distilled water just before administration to the animals by gavage.The Paxilline(2.5 mg·kg-1;ip)was administered 10min beforeEt OH-PC and NS11021-PC.The right middle cerebral artery occlusion(MCAO)was produced by inversion of a 4-0-nylon filament.The filament was withdrawn 2 h after onset of MCAO and then reperfused.Neurological deficits and infarct volume were measured 24 h after I/R.Another 36 rats were randomly divided into 6 groups as above,6 in each group.DWI were performed 2h after ischemic and T2WI MRI were performed 24 h after I/R to observe the infarct volume of brain and the penumbra volume of brain in each group.Then rats were killed and detected the apoptotic cell death and degeneration of neurons.RESULTS Compared to I/R group,the neurological score(P<0.01),the infarct volume of brain(P<0.01),the infarct volume of ischemic penumbra(P<0.01),the percentage of apoptotic cell death(P<0.01)and the percentage of degenerative neurons(P<0.01)were significantly decreased after ethanol preconditioning,while these changes were reversed by paxilline(P<0.05);compared to I/R group,the neurological score(P<0.01),the infarct volume of brain(P<0.01),the infarct volume of ischemic penumbra(P<0.01),the percentage of apoptotic cell death(P<0.01)and the percentage of degenerative neurons(P<0.01)were significantly decreased after NS11021 preconditioning,while these changes were reversed by paxilline(P<0.05).CONCLUSION Our results show that moderate alcohol preconditioning activates BKCa channels to protect brain damage induced by focal cerebral I/R.

Using eye movements in the dot-probe paradigm to investigate attention bias in illness anxiety disorder

BACKGROUND Illness anxiety disorder(IAD)is a common,distressing,and debilitating condition with the key feature being a persistent conviction of the possibility of having one or more serious or progressive physical disorders.Because eye movements are guided by visual-spatial attention,eye-tracking technology is a comparatively direct,continuous measure of attention direction and speed when stimuli are oriented.Researchers have tried to identify selective visual attention biases by tracking eye movements within dot-probe paradigms because dot-probe paradigm can distinguish these attentional biases more clearly.AIM To examine the association between IAD and biased processing of illness-related information.METHODS A case-control study design was used to record eye movements of individuals with IAD and healthy controls while participants viewed a set of pictures from four categories(illness-related,socially threatening,positive,and neutral images).Biases in initial orienting were assessed from the location of the initial shift in gaze,and biases in the maintenance of attention were assessed from the duration of gaze that was initially fixated on the picture per image category.RESULTS The eye movement of the participants in the IAD group was characterized by an avoidance bias in initial orienting to illness-related pictures.There was no evidence of individuals with IAD spending significantly more time viewing illness-related images compared with other images.Patients with IAD had an attention bias at the early stage and overall attentional avoidance.In addition,this study found that patients with significant anxiety symptoms showed attention bias in the late stages of attention processing.CONCLUSION Illness-related information processing biases appear to be a robust feature of IAD and may have an important role in explaining the etiology and maintenance of the disorder.

Hyaluronic acid hydrogel: a promising scaffold for restoration in the central nervous system

Injury in the central nervous system (CNS), stroke in the brain and trauma in the spinal cord in particular, may result in permanent disability of the patients, since CNS axons do not regenerate appreciably in their native environment due to several inhibitory molecules in the extracellular environment. Therefore, no effective clinical therapies so far are convincingly accepted for CNS injuries. Tissue engineering strategies employing biomaterials are now considered as a promising approach for restoration of these injuries, and hydrogel-based biomaterials are widely employed in this field. Among them, many studies have proven that hyaluronic acid (HA) hydrogel is a reliable and effective biomaterial, which can be a well compatible scaffold with CNS tissue and creating a good microenvironment of neural regeneration in the CNS tissue. The aim of this review is to outline how to use HA-based scaffolds to build up a suitable microenvironment of neural regeneration and restoration after CNS injury, and thereby to indicate the HA hydrogel is a promising scaffold for restoration in the CNS.