β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unkno...β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.展开更多
Fast and efficient transmission of electrical signals in the nervous system is mediated through myelinated nerve fibers.In neuronal diseases such as multiple sclerosis,the conduction properties of axons are disturbed ...Fast and efficient transmission of electrical signals in the nervous system is mediated through myelinated nerve fibers.In neuronal diseases such as multiple sclerosis,the conduction properties of axons are disturbed by the removal of the myelin sheath,leaving nerve cells at a higher risk of degenerating.In some cases,the protective myelin sheath of axons can be rebuilt by remyelination through oligodendroglial cells.In any case,however,changes in the ion channel organization occur and may help to restore impulse conduction after demyelination.On the other hand,changes in ion channel distribution may increase the energy demand of axons,thereby increasing the probability of axonal degeneration.Many attempts have been made or discussed in recent years to increase remyelination of affected axons in demyelinating diseases such as multiple sclerosis.These approaches range from pharmacological treatments that reduce inflammatory processes or block ion channels to the modulation of neuronal activity through electrical cortical stimulation.However,these treatments either affect the entire organism(pharmacological)or exert a very local effect(electrodes).Current results show that neuronal activity is a strong regulator of oligodendroglial development.To bridge the gap between global and very local treatments,non-invasive transcranial magnetic stimulation could be considered.Transcranial magnetic stimulation is externally applied to brain areas and experiments with repetitive transcranial magnetic stimulation show that the neuronal activity can be modulated depending on the stimulation parameters in both humans and animals.In this review,we discuss the possibilities of influencing ion channel distribution and increasing neuronal activity by transcranial magnetic stimulation as well as the effect of this modulation on oligodendroglial cells and their capacity to remyelinate previously demyelinated axons.Although the physiological mechanisms underlying the effects of transcranial magnetic stimulation clearly need further investigations,repetitive transcranial magnetic stimulation may be a promising approach for non-invasive neuronal modulation aiming at enhancing remyelination and thus reducing neurodegeneration.展开更多
Objective: To find out an effective fixative in immunohistochemistry for high-affinity neurotrophin receptor-tyrosine kinase (Trk) B. Methods: Comparing the results from four groups of adult rats which were fixed by d...Objective: To find out an effective fixative in immunohistochemistry for high-affinity neurotrophin receptor-tyrosine kinase (Trk) B. Methods: Comparing the results from four groups of adult rats which were fixed by different fixatives before the brain sections were processed for TrkB immunohistochemistry. Results: In the four groups, TrkB immunoreactive cells were observed throughout the whole brain, but the intensity of immunoreactive cells and the background staining exhibited a marked difference among the groups. Conclusion: Using 0.3%-0.5% paraformaldehyde in 75% saturated picric acid 0.1 mol/L di-sodium hydrogen phosphate buffer as the fixative may yield the best quality of TrkB immunoreactivity.展开更多
Objectives: Iodine deficiency (ID) is a common cause of preventable brain damage and mental retardation worldwide, according to the World Health Organisation. It may adversely affect brain maturation processes that po...Objectives: Iodine deficiency (ID) is a common cause of preventable brain damage and mental retardation worldwide, according to the World Health Organisation. It may adversely affect brain maturation processes that potentially result in structural and metabolic brain abnormalities, visible on Magnetic Resonance (MR) techniques. Currently, however, there has been no review of the appearance of these brain changes on MR methods. Methods: A systematic review was conducted using 3 online search databases (Medline, Embase and Web of Knowledge) using multiple combinations of the following search terms: iodine, iodine deficiency, magnetic resonance, MRI, MRS, brain, imaging and iodine deficiency disorders (i.e. hypothyroxinaemia, congenital hypothyroidism, hypothyroidism and cretinism). Results: Up to May 2013, 1673 related papers were found. Of these, 29 studies confirmed their findings directly using MR Imaging and/or MR Spectroscopy. Of them, 28 were in humans and involved 157 subjects, 46 of whom had primary hypothyroidism, 97 had congenital hypothyroidism, 3 had endemic cretinism and 11 had subclinical hypothyroidism. The studies were small, with a mean relevant sample size of 6, median 2, range 1 - 35, while 14 studies were individual case reports. T1-weighted was the most commonly used MRI sequence (20/29 studies) and 1.5 Tesla was the most commonly used magnet strength (6/10 studies that provided this information). Pituitary abnormalities (18/29 studies) and cerebellar atrophy (3/29 studies) were the most prevalent brain abnormalities found. Only fMRI studies (3/29) reported cognition-related abnormalities but the brain changes found were limited to a visual description in all studies. Conclusions: More studies that use MR methods to identify changes on brain volume or other global structural abnormalities and explain the mechanism of ID causing thyroid dysfunction and hence cognitive damage are required. Given the role of MR techniques in cognitive studies, this review provides a starting point for researching the macroscopic structural brain changes caused by ID.展开更多
A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro,suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regen...A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro,suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regeneration.However,in vivo experiments have not been conducted.In this study,we transplanted a hyaluronic acid granular hydrogel nerve guidance conduit to repair a 10-mm long sciatic nerve gap.The Basso,Beattie,and Bresnahan locomotor rating scale,sciatic nerve compound muscle action potential recording,Fluoro-Gold retrograde tracing,growth related protein 43/S100 immunofluorescence staining,transmission electron microscopy,gastrocnemius muscle dry/wet weight ratio,and Masson’s trichrome staining results showed that the nerve guidance conduit exhibited similar regeneration of sciatic nerve axons and myelin sheath,and recovery of the electrophysiological function and motor function as autologous nerve transplantation.The conduit results were superior to those of a bulk hydrogel or silicone tube transplant.These findings suggest that tissue-engineered nerve conduits containing hyaluronic acid granular hydrogels effectively promote the morphological and functional recovery of the injured sciatic nerve.The nerve conduits have the potential as a material for repairing peripheral nerve defects.展开更多
Brain damage sustained from repeated blows in boxing, wrestling, and other combat sports has serious physical and mental health consequences. The degenerative brain disease, chronic traumatic encephalopathy (CTE), pre...Brain damage sustained from repeated blows in boxing, wrestling, and other combat sports has serious physical and mental health consequences. The degenerative brain disease, chronic traumatic encephalopathy (CTE), presents clinically with memory loss, aggression, difficulty in rational thinking and other cognitive problems. This spectrum, which mimics Alzheimer’s disease, is diagnosed post-mortem through a brain biopsy in many professional athletes. However, little is known about the process of development and how to identify vulnerable individuals who may be on course for developing CTE. Boxing is a sport that has a severe toll on athletes’ health, primarily on their brain health and function. This review addresses the concerns of brain injury, describes the pathologies that manifest in multiple scales, e.g., molecular and cognitive, and also proposes possible diagnostic and prognostic markers to characterize the early onset of CTE along with the aim to identify a starting point for future precautions and interventions.展开更多
Brain-derived neurotrophic factor(BDNF),a critical neurotrophin,regulates many neuronal aspects including cell differentiation,cell survival,neurotransmission,and synaptic plasticity in the central nervous system(CNS)...Brain-derived neurotrophic factor(BDNF),a critical neurotrophin,regulates many neuronal aspects including cell differentiation,cell survival,neurotransmission,and synaptic plasticity in the central nervous system(CNS) .Though BDNF has two types of receptors,high affinity tropomyosin-related kinase(Trk) B and low affinity p75 receptors,BDNF positively exerts its biological effects on neurons via activation of TrkB and of resultant intracellular signaling cascades including mitogenactivated protein kinase/extracellular signal-regulated protein kinase,phospholipase Cγ,and phosphoinositide 3-kinase pathways.Notably,it is possible that alteration in the expression and/or function of BDNF in the CNS is involved in the pathophysiology of various brain diseases such as stroke,Parkinson's disease,Alzheimer's disease,and mental disorders.On the other hand,glucocorticoids,stress-induced steroid hormones,also putatively contribute to the pathophysiology of depression.Interestingly,in addition to the reduction in BDNF levels due to increased glucocorticoid exposure,current reports demonstrate possible interactions between glucocorticoids and BDNF-mediated neuronal functions. Other steroid hormones,such as estrogen,are involved in not only sexual differentiation in the brain,but also numerous neuronal events including cell survival and synaptic plasticity.Furthermore,it is well known that estrogen plays a role in the pathophysiology of Parkinson's disease,Alzheimer's disease,and mental illness,while serving to regulate BDNF expression and/or function.Here,we present a broad overview of the current knowledge concerning the association between BDNF expression/function and steroid hormones(glucocorticoids and estrogen).展开更多
Neuroinformatics is a fascinating research field that applies computational models and analytical tools to high dimensional experimental neuroscience data for a better understanding of how the brain functions or dysfu...Neuroinformatics is a fascinating research field that applies computational models and analytical tools to high dimensional experimental neuroscience data for a better understanding of how the brain functions or dysfunctions in brain diseases. Neuroinformaticians work in the intersection of neuroscience and informatics supporting the integration of various sub-disciplines(behavioural neuroscience, genetics, cognitive psychology, etc.) working on brain research. Neuroinformaticians are the pathway of information exchange between informaticians and clinicians for a better understanding of the outcome of computational models and the clinical interpretation of the analysis. Machine learning is one of the most significant computational developments in the last decade giving tools to neuroinformaticians and finally to radiologists and clinicians for an automatic and early diagnosis-prognosis of a brain disease. Random forest(RF) algorithm has been successfully applied to high-dimensional neuroimaging data for feature reduction and also has been applied to classify the clinical label of a subject using single or multi-modal neuroimaging datasets. Our aim was to review the studies where RF was applied to correctly predict the Alzheimer's disease(AD), the conversion from mild cognitive impairment(MCI) and its robustness to overfitting, outliers and handling of non-linear data. Finally, we described our RF-based model that gave us the 1 ^(st) position in an international challenge for automated prediction of MCI from MRI data.展开更多
Naproxen(NP), a nonsteroidal anti-inflammatory drug(NSAID), is used for the treatment of common pain, inflammation and tissue damage. Genotoxicity testing of NP is of prime importance as it represents the largest grou...Naproxen(NP), a nonsteroidal anti-inflammatory drug(NSAID), is used for the treatment of common pain, inflammation and tissue damage. Genotoxicity testing of NP is of prime importance as it represents the largest group of drugs to which humans are exposed. Not many genotoxic studies are reported on NP;therefore, the present study investigated the detailed genotoxic and oxidative stress properties of NP.Male Wistar rats were administered NP orally at the doses of 38.91 and 65.78 mg/kg body weight for 14 days. Reduced glutathione(GSH), superoxide dismutase(SOD), catalase(CAT) and lipid peroxidation(LPO) activities/levels were measured in the liver, kidney and brain tissues. The aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP) activities, and total bilirubin(TBIL) levels were measured in the liver tissues. Micronucleus frequency(micronucleus test MNT)and DNA damage(comet assay) were performed in the bone marrow cells and leukocytes, respectively.The results showed that NP treatment decreased the GSH levels and increased the SOD, CAT, LPO, ALT,AST, ALP and TBIL activities/levels compared to the control(p o 0.05). Results of MNT showed an increased micronucleus induction and comet assay showed a significant increase in DNA damage in the NP treated animals(p o 0.05). Treatment of NP resulted in the biochemical imbalance and induced oxidative stress that deteriorated the integrity of the cells, which caused significant damage to the genetic material and affected liver function in male Wistar rats. Therefore, NP is a potential genotoxic agent that induces genotoxicity and oxidative stress.展开更多
BACKGROUND Central sensitization plays a pivotal role in the maintenance of chronic pain induced by chronic pancreatitis(CP).We hypothesized that the nucleus tractus solitarius(NTS),a primary central site that integra...BACKGROUND Central sensitization plays a pivotal role in the maintenance of chronic pain induced by chronic pancreatitis(CP).We hypothesized that the nucleus tractus solitarius(NTS),a primary central site that integrates pancreatic afferents apart from the thoracic spinal dorsal horn,plays a key role in the pathogenesis of visceral hypersensitivity in a rat model of CP.AIM To investigate the role of the NTS in the visceral hypersensitivity induced by chronic pancreatitis.METHODS CP was induced by the intraductal injection of trinitrobenzene sulfonic acid(TNBS)in rats.Pancreatic hyperalgesia was assessed by referred somatic pain via von Frey filament assay.Neural activation of the NTS was indicated by immunohistochemical staining for Fos.Basic synaptic transmission within the NTS was assessed by electrophysiological recordings.Expression of vesicular glutamate transporters(VGluTs),N-methyl-D-aspartate receptor subtype 2B(NR2B),andα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subtype 1(GluR1)was analyzed by immunoblotting.Membrane insertion of NR2B and GluR1 was evaluated by electron microscopy.The regulatory role of the NTS in visceral hypersensitivity was detected via pharmacological approach and chemogenetics in CP rats.RESULTS TNBS treatment significantly increased the number of Fos-expressing neurons within the caudal NTS.The excitatory synaptic transmission was substantially potentiated within the caudal NTS in CP rats(frequency:5.87±1.12 Hz in CP rats vs 2.55±0.44 Hz in sham rats,P<0.01;amplitude:19.60±1.39 pA in CP rats vs 14.71±1.07 pA in sham rats;P<0.01).CP rats showed upregulated expression of VGluT2,and increased phosphorylation and postsynaptic trafficking of NR2B and GluR1 within the caudal NTS.Blocking excitatory synaptic transmission via the AMPAR antagonist CNQX and the NMDAR antagonist AP-5 microinjection reversed visceral hypersensitivity in CP rats(abdominal withdraw threshold:7.00±1.02 g in CNQX group,8.00±0.81 g in AP-5 group and 1.10±0.27 g in saline group,P<0.001).Inhibiting the excitability of NTS neurons via chemogenetics also significantly attenuated pancreatic hyperalgesia(abdominal withdraw threshold:13.67±2.55 g in Gi group,2.00±1.37 g in Gq group,and 2.36±0.67 g in mCherry group,P<0.01).CONCLUSION Our findings suggest that enhanced excitatory transmission within the caudal NTS contributes to pancreatic pain and emphasize the NTS as a pivotal hub for the processing of pancreatic afferents,which provide novel insights into the central sensitization of painful CP.展开更多
Objective Aims to delineate the distribution profile of three isoforms of vesicular glutamate transporter (VGluT), viz. VGluT1-3, and their cellular localization within vestibular nuclear complex (VNC). Methods Br...Objective Aims to delineate the distribution profile of three isoforms of vesicular glutamate transporter (VGluT), viz. VGluT1-3, and their cellular localization within vestibular nuclear complex (VNC). Methods Brain sections from normal Sprague-Dawley rats were processed immunohistochemically for VGluT detection, employing avidinbiotinylated peroxidase complex method with 3-3'-diaminobenzidine (DAB) as chromogen. Results The whole VNC expressed all of the three transporters that were observed to be localized to the fiber endings. Compared with VGluT1 and VGluT3, VGluT2 demonstrated a relatively homogeneous distribution, with much higher density in VNC. VGluT3 displayed the highest density in lateral vestibular nucleus and group X, contrasting with the sparse immunostained puncta within vestibular medial and inferior nuclei. Conclusion Glutamtatergic pathways participate in the processing of vestibular signals within VNC mainly through the re-uptake of glutamate into synaptic vesicles by VGluT1 and 2, whereas VGluT3 may play a similar role mainly in areas other than medial and inferior nuclei of VNC.展开更多
The pathogenesis of temporal lobe epilepsy(TLE)was originally considered to be acquired.However,some reports showed that TLE was clustered in some families,indicating a genetic etiology.With the popularity of genetic ...The pathogenesis of temporal lobe epilepsy(TLE)was originally considered to be acquired.However,some reports showed that TLE was clustered in some families,indicating a genetic etiology.With the popularity of genetic testing technology,eleven different types of familial TLE(FTLE),including ETL1-ETL11,have been reported,of which ETL9-ETL11 had not yet been included in the OMIM database.These types of FTLE were caused by different genes/Loci and had distinct characteristics.ETL1,ETL7 and ETL10 were characterized by auditory,visual and aphasia seizures,leading to the diagnosis of familial lateral TLE.ETL2,ETL3 and ETL6 showed prominent autonomic symptom and automatism with or without hippocampal abnormalities,indicating a mesial temporal origin.Febrile seizures were common in FTLEs such as ETL2,ETL5,ETL6 and ETL11.ETL4 was diagnosed as occipitotemporal lobe epilepsy with a high incidence of migraine and visual aura.Considering the diversity and complexity of the symptoms of TLE,neurologists enquiring about the family history of epilepsy should ask whether the relatives of the proband had experienced unnoticeable seizures and whether there is a family history of other neurological diseases carefully.Most FTLE patients had a good prognosis with or without anti-seizure medication treatment,with the exception of patients with heterozygous mutations of the CPA6 gene.The pathogenic mechanism was diverse among these genes and spans disturbances of neuron development,differentiation and synaptic signaling.In this article,we describe the research progress on eleven different types of FTLE.The precise molecular typing of FTLE would facilitate the diagnosis and treatment of FTLE and genetic counseling for this disorder.展开更多
AIM:To investigate the distribution and neurochemical phenotype of endomorphin-2(EM-2)-containing neurons in the submucosal plexus of the rat colon.METHODS:The mid-colons between the right and left flexures were remov...AIM:To investigate the distribution and neurochemical phenotype of endomorphin-2(EM-2)-containing neurons in the submucosal plexus of the rat colon.METHODS:The mid-colons between the right and left flexures were removed from rats,and transferred into Kreb's solution. For whole-mount preparations,the mucosal,outer longitudinal muscle and inner circularmuscle layers of the tissues were separated from the submucosal layer attached to the submucosal plexus. The whole-mount preparations from each rat mid-colon were mounted onto seven gelatin-coated glass slides,and processed for immunofluorescence histochemical double-staining of EM-2 with calcitonin gene-related peptide(CGRP),choline acetyltransferase(Ch AT),nitric oxide synthetase(NOS),neuron-specific enolase(NSE),substance P(SP) and vasoactive intestinal peptide(VIP). After staining,all the fluorescence-labeled sections were observed with a confocal laser scanning microscope. To estimate the extent of the co-localization of EM-2 with CGRP,Ch AT,NOS,NSE,SP and VIP,ganglia,which have a clear boundary and neuronal cell outline,were randomly selected from each specimen for this analysis. RESULTS:In the submucosal plexus of the mid-colon,many EM-2-immunoreactive(IR) and NSE-IR neuronal cell bodies were found in the submucosal plexus of the rat mid-colon. Approximately 6 ± 4.2 EM-2-IR neurons aggregated within each ganglion and a few EM-2-IR neurons were also found outside the ganglia. The EM-2-IR neurons were also immunopositive for Ch AT,SP,VIP or NOS. EM-2-IR nerve fibers coursed near Ch AT-IR neurons,and some of these fibers were even distributed around Ch AT-IR neuronal cell bodies. Some EM-2-IR neuronal cell bodies were surrounded by SP-IR nerve fibers,but many long processes connecting adjacent ganglia were negative for EM-2 immunostaining. Long VIP-IR processes with many branches coursed through the ganglia and surrounded the EM-2-IR neurons. The percentages of the EM-2-IR neurons that were also positive for Ch AT,SP,VIP or NOS were approximately 91% ± 2.6%,36% ± 2.4%,44% ± 2.5% and 44% ± 4.7%,respectively,but EM-2 did not co-localize with CGRP. CONCLUSION:EM-2-IR neurons are present in the submucosal plexus of the rat colon and express distinct neurochemical markers.展开更多
GABAergic neurons are the major inhibitory interneurons that powerfully control the function of spinal neuronal networks.In recent years,tremendous progresses have been made in understanding the transcriptional contro...GABAergic neurons are the major inhibitory interneurons that powerfully control the function of spinal neuronal networks.In recent years,tremendous progresses have been made in understanding the transcriptional control of GABAergic neuron development in the dorsal spinal cord.New experimental approaches provide a relatively high throughput way to study the molecular regulation of subgroup fate determination.Our understanding of the molecular mechanisms on GABAergic neuron development in the dorsal spinal cord is rapidly expanding.Recent studies have defined several transcription factors that play essential roles in GABAergic neuron development in the spinal dorsal horn.Here,we review results of very recent analyses of the mechanisms that specify the GABAergic neuron development in the dorsal spinal cord,especially the progresses in the homeodomain(HD) and basic-helix-loop-helix(bHLH) containing transcription factors.展开更多
Ventral tegmental area(VTA),which is well-documented as a modulatory center of reward and addiction,has been demonstrated to participate in pain processing.In addition,insula cortex(IC)has also been proved to be relat...Ventral tegmental area(VTA),which is well-documented as a modulatory center of reward and addiction,has been demonstrated to participate in pain processing.In addition,insula cortex(IC)has also been proved to be related with maintenance of neuropathic pain.In the present study,in order to clarify whether there exist dopaminergic projections from the VTA to the IC,retrograde and anterograde tracing methods combined with immunofluorescent histochemical staining were applied.The results revealed that almost all VTA-IC-projecting neurons originated from the VTA were dopaminergic neurons,with smaller amount of GABAergic neurons sending projection fiberss to the IC.展开更多
Ventral lateral periaqueductal gray(vIPAG)is an essential transmit node in descending transmission pathway.However,whether neurons expressing different receptors in vIPAG paly distinct roles in nociception and prurice...Ventral lateral periaqueductal gray(vIPAG)is an essential transmit node in descending transmission pathway.However,whether neurons expressing different receptors in vIPAG paly distinct roles in nociception and pruriception remains elusive.To evaluate the possible effects of different neuroactive substances in vlPAG,cannula was implanted in the right side of the vIPAG.In the present study,a-amino 3-hydroxy-5-methyl-4-isoxazole-propionic acid(AMPA)receptor antagonist CNQX,N-methyl-D-aspartic acid(NMDA)receptor antagonist AP-5,Y-aminobutyric acid A(GABAs)receptor antagonist picrotoxin(PTX),μ-opioid receptor antagonist CTOP and calcitonin gene-related peptide(CGRP)antagonist CGRP8-37 were utilized.展开更多
Central sensitization plays a pivotal role in the maintenance of chronic pain induced byvisceral diseases,including chronic pancreatitis(CP),but cortical modulation of painful CP remains elusive.This study was designe...Central sensitization plays a pivotal role in the maintenance of chronic pain induced byvisceral diseases,including chronic pancreatitis(CP),but cortical modulation of painful CP remains elusive.This study was designed to examine the role of anterior insular cortex(aIC)in the pathogenesis of visceral hypersensitivity in a rat model of CP.CP was induced by intraductal administration of trinitrobenzene sulfonic acid(TNBS).Visceral hypersensitivity and anxiety were assessed by von Frey filament examination and open field test,respectively.Two weeks after surgery,neural activation within aIC was tested by both examining Fos expression and electrophysiological recordings.Expressions of VGluT1,NMDAR subunit NR2B and AMPAR subunit GluR1 were analyzed by immunoblottings.The regulatory roles of aIC in visceral hypersensitivity and pain-related anxiety were detected via pharmacological approach and chemogenetic test in CP rats.展开更多
Central sensitizationis critical for chronic pain sensation induced by chronic pancreatitis(CP).We hypothesized that the nucleus tractus solitarius(NTS),a primary central site that integrates pancreatic afferents apar...Central sensitizationis critical for chronic pain sensation induced by chronic pancreatitis(CP).We hypothesized that the nucleus tractus solitarius(NTS),a primary central site that integrates pancreatic afferents apart from the thoracic spinal dorsal horn,plays a key role in the pathogenesis of visceral hypersensitivity in a rat model of CP.In order to investigate the role of the NTS in the visceral hypersensitivity induced by chronic pancreatitis,CP was induced by the intraductal injection of trinitrobenzene sulfonic acid(TNBS)in rats.Pancreatic hyperalgesia was assessed by referred somatic pain via von Frey filament assay.Neural activation of the NTS was indicated by Fos-immunohistochemical staining.展开更多
Diabetic mechanical allodynia(DMA)remains no effective treatment currently.TRPV4 is involved in mechanical sensation of varying etiologies,but expression feature and the whether it contributes to the DMA are so far un...Diabetic mechanical allodynia(DMA)remains no effective treatment currently.TRPV4 is involved in mechanical sensation of varying etiologies,but expression feature and the whether it contributes to the DMA are so far unclear.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82104158(to XT),31800887(to LY),31972902(to LY),82001422(to YL)China Postdoctoral Science Foundation,No.2020M683750(to LY)partially by Young Talent Fund of University Association for Science and Technology in Shaanxi Province of China,No.20200307(to LY).
文摘β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.
基金supported by the DFG BE 6048/2-1(to AB)and DFG PF574/5-1(to FP)。
文摘Fast and efficient transmission of electrical signals in the nervous system is mediated through myelinated nerve fibers.In neuronal diseases such as multiple sclerosis,the conduction properties of axons are disturbed by the removal of the myelin sheath,leaving nerve cells at a higher risk of degenerating.In some cases,the protective myelin sheath of axons can be rebuilt by remyelination through oligodendroglial cells.In any case,however,changes in the ion channel organization occur and may help to restore impulse conduction after demyelination.On the other hand,changes in ion channel distribution may increase the energy demand of axons,thereby increasing the probability of axonal degeneration.Many attempts have been made or discussed in recent years to increase remyelination of affected axons in demyelinating diseases such as multiple sclerosis.These approaches range from pharmacological treatments that reduce inflammatory processes or block ion channels to the modulation of neuronal activity through electrical cortical stimulation.However,these treatments either affect the entire organism(pharmacological)or exert a very local effect(electrodes).Current results show that neuronal activity is a strong regulator of oligodendroglial development.To bridge the gap between global and very local treatments,non-invasive transcranial magnetic stimulation could be considered.Transcranial magnetic stimulation is externally applied to brain areas and experiments with repetitive transcranial magnetic stimulation show that the neuronal activity can be modulated depending on the stimulation parameters in both humans and animals.In this review,we discuss the possibilities of influencing ion channel distribution and increasing neuronal activity by transcranial magnetic stimulation as well as the effect of this modulation on oligodendroglial cells and their capacity to remyelinate previously demyelinated axons.Although the physiological mechanisms underlying the effects of transcranial magnetic stimulation clearly need further investigations,repetitive transcranial magnetic stimulation may be a promising approach for non-invasive neuronal modulation aiming at enhancing remyelination and thus reducing neurodegeneration.
文摘Objective: To find out an effective fixative in immunohistochemistry for high-affinity neurotrophin receptor-tyrosine kinase (Trk) B. Methods: Comparing the results from four groups of adult rats which were fixed by different fixatives before the brain sections were processed for TrkB immunohistochemistry. Results: In the four groups, TrkB immunoreactive cells were observed throughout the whole brain, but the intensity of immunoreactive cells and the background staining exhibited a marked difference among the groups. Conclusion: Using 0.3%-0.5% paraformaldehyde in 75% saturated picric acid 0.1 mol/L di-sodium hydrogen phosphate buffer as the fixative may yield the best quality of TrkB immunoreactivity.
文摘Objectives: Iodine deficiency (ID) is a common cause of preventable brain damage and mental retardation worldwide, according to the World Health Organisation. It may adversely affect brain maturation processes that potentially result in structural and metabolic brain abnormalities, visible on Magnetic Resonance (MR) techniques. Currently, however, there has been no review of the appearance of these brain changes on MR methods. Methods: A systematic review was conducted using 3 online search databases (Medline, Embase and Web of Knowledge) using multiple combinations of the following search terms: iodine, iodine deficiency, magnetic resonance, MRI, MRS, brain, imaging and iodine deficiency disorders (i.e. hypothyroxinaemia, congenital hypothyroidism, hypothyroidism and cretinism). Results: Up to May 2013, 1673 related papers were found. Of these, 29 studies confirmed their findings directly using MR Imaging and/or MR Spectroscopy. Of them, 28 were in humans and involved 157 subjects, 46 of whom had primary hypothyroidism, 97 had congenital hypothyroidism, 3 had endemic cretinism and 11 had subclinical hypothyroidism. The studies were small, with a mean relevant sample size of 6, median 2, range 1 - 35, while 14 studies were individual case reports. T1-weighted was the most commonly used MRI sequence (20/29 studies) and 1.5 Tesla was the most commonly used magnet strength (6/10 studies that provided this information). Pituitary abnormalities (18/29 studies) and cerebellar atrophy (3/29 studies) were the most prevalent brain abnormalities found. Only fMRI studies (3/29) reported cognition-related abnormalities but the brain changes found were limited to a visual description in all studies. Conclusions: More studies that use MR methods to identify changes on brain volume or other global structural abnormalities and explain the mechanism of ID causing thyroid dysfunction and hence cognitive damage are required. Given the role of MR techniques in cognitive studies, this review provides a starting point for researching the macroscopic structural brain changes caused by ID.
基金supported by the National Natural Science Foundation of China,Nos.81620108008(to YQL),31971112(to YQL),82071373(to JC)Innovation Capability Support Program of Shaanxi,No.2021TD-57(to YQL)。
文摘A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro,suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regeneration.However,in vivo experiments have not been conducted.In this study,we transplanted a hyaluronic acid granular hydrogel nerve guidance conduit to repair a 10-mm long sciatic nerve gap.The Basso,Beattie,and Bresnahan locomotor rating scale,sciatic nerve compound muscle action potential recording,Fluoro-Gold retrograde tracing,growth related protein 43/S100 immunofluorescence staining,transmission electron microscopy,gastrocnemius muscle dry/wet weight ratio,and Masson’s trichrome staining results showed that the nerve guidance conduit exhibited similar regeneration of sciatic nerve axons and myelin sheath,and recovery of the electrophysiological function and motor function as autologous nerve transplantation.The conduit results were superior to those of a bulk hydrogel or silicone tube transplant.These findings suggest that tissue-engineered nerve conduits containing hyaluronic acid granular hydrogels effectively promote the morphological and functional recovery of the injured sciatic nerve.The nerve conduits have the potential as a material for repairing peripheral nerve defects.
文摘Brain damage sustained from repeated blows in boxing, wrestling, and other combat sports has serious physical and mental health consequences. The degenerative brain disease, chronic traumatic encephalopathy (CTE), presents clinically with memory loss, aggression, difficulty in rational thinking and other cognitive problems. This spectrum, which mimics Alzheimer’s disease, is diagnosed post-mortem through a brain biopsy in many professional athletes. However, little is known about the process of development and how to identify vulnerable individuals who may be on course for developing CTE. Boxing is a sport that has a severe toll on athletes’ health, primarily on their brain health and function. This review addresses the concerns of brain injury, describes the pathologies that manifest in multiple scales, e.g., molecular and cognitive, and also proposes possible diagnostic and prognostic markers to characterize the early onset of CTE along with the aim to identify a starting point for future precautions and interventions.
基金Supported by Research Grants for Nervous and Mental Disorders from the Ministry of Health,Labor and Welfare Health and Labor Sciences Research Grants (Research on Psychiatric and Neurological Diseases and Mental Health)+2 种基金Health and Labor Sciences Research Grants,a grant from the Japan Foundation for Neuroscience and Mental Healththe Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (Kunugi H)a Grant-in-Aid for Young Scientists (A) (21680034) from the Ministry of Education,Culture,Sports,Science,and Technology of Japan (Numakawa T)
文摘Brain-derived neurotrophic factor(BDNF),a critical neurotrophin,regulates many neuronal aspects including cell differentiation,cell survival,neurotransmission,and synaptic plasticity in the central nervous system(CNS) .Though BDNF has two types of receptors,high affinity tropomyosin-related kinase(Trk) B and low affinity p75 receptors,BDNF positively exerts its biological effects on neurons via activation of TrkB and of resultant intracellular signaling cascades including mitogenactivated protein kinase/extracellular signal-regulated protein kinase,phospholipase Cγ,and phosphoinositide 3-kinase pathways.Notably,it is possible that alteration in the expression and/or function of BDNF in the CNS is involved in the pathophysiology of various brain diseases such as stroke,Parkinson's disease,Alzheimer's disease,and mental disorders.On the other hand,glucocorticoids,stress-induced steroid hormones,also putatively contribute to the pathophysiology of depression.Interestingly,in addition to the reduction in BDNF levels due to increased glucocorticoid exposure,current reports demonstrate possible interactions between glucocorticoids and BDNF-mediated neuronal functions. Other steroid hormones,such as estrogen,are involved in not only sexual differentiation in the brain,but also numerous neuronal events including cell survival and synaptic plasticity.Furthermore,it is well known that estrogen plays a role in the pathophysiology of Parkinson's disease,Alzheimer's disease,and mental illness,while serving to regulate BDNF expression and/or function.Here,we present a broad overview of the current knowledge concerning the association between BDNF expression/function and steroid hormones(glucocorticoids and estrogen).
基金supported by Medical Research Council(MRC)grant MR/K004360/1 to SIDMARIE CURIE COFUND EU-UK Research Fellowship to SID
文摘Neuroinformatics is a fascinating research field that applies computational models and analytical tools to high dimensional experimental neuroscience data for a better understanding of how the brain functions or dysfunctions in brain diseases. Neuroinformaticians work in the intersection of neuroscience and informatics supporting the integration of various sub-disciplines(behavioural neuroscience, genetics, cognitive psychology, etc.) working on brain research. Neuroinformaticians are the pathway of information exchange between informaticians and clinicians for a better understanding of the outcome of computational models and the clinical interpretation of the analysis. Machine learning is one of the most significant computational developments in the last decade giving tools to neuroinformaticians and finally to radiologists and clinicians for an automatic and early diagnosis-prognosis of a brain disease. Random forest(RF) algorithm has been successfully applied to high-dimensional neuroimaging data for feature reduction and also has been applied to classify the clinical label of a subject using single or multi-modal neuroimaging datasets. Our aim was to review the studies where RF was applied to correctly predict the Alzheimer's disease(AD), the conversion from mild cognitive impairment(MCI) and its robustness to overfitting, outliers and handling of non-linear data. Finally, we described our RF-based model that gave us the 1 ^(st) position in an international challenge for automated prediction of MCI from MRI data.
基金supported by grants from DBT NER (BT/ PR16164/NER/95/88/2015)DST PURSE-(Phase-Ⅱ)(PAC-JNU-DSTPURSE-462)UGC RNW,UGC SAP at the level of DRS-Ⅰ & Ⅱ,and UPE-Ⅱ,JNU(Project Id No. 247)
文摘Naproxen(NP), a nonsteroidal anti-inflammatory drug(NSAID), is used for the treatment of common pain, inflammation and tissue damage. Genotoxicity testing of NP is of prime importance as it represents the largest group of drugs to which humans are exposed. Not many genotoxic studies are reported on NP;therefore, the present study investigated the detailed genotoxic and oxidative stress properties of NP.Male Wistar rats were administered NP orally at the doses of 38.91 and 65.78 mg/kg body weight for 14 days. Reduced glutathione(GSH), superoxide dismutase(SOD), catalase(CAT) and lipid peroxidation(LPO) activities/levels were measured in the liver, kidney and brain tissues. The aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP) activities, and total bilirubin(TBIL) levels were measured in the liver tissues. Micronucleus frequency(micronucleus test MNT)and DNA damage(comet assay) were performed in the bone marrow cells and leukocytes, respectively.The results showed that NP treatment decreased the GSH levels and increased the SOD, CAT, LPO, ALT,AST, ALP and TBIL activities/levels compared to the control(p o 0.05). Results of MNT showed an increased micronucleus induction and comet assay showed a significant increase in DNA damage in the NP treated animals(p o 0.05). Treatment of NP resulted in the biochemical imbalance and induced oxidative stress that deteriorated the integrity of the cells, which caused significant damage to the genetic material and affected liver function in male Wistar rats. Therefore, NP is a potential genotoxic agent that induces genotoxicity and oxidative stress.
基金Supported by National Natural Science Foundation of China,No.81620108008Major Research and Development Project of Hainan Province,No.2018153 to Yun-Qing LiTraining Program for Scientific Research Scholars of Fujian Provincial Health and Family Planning Commission,No.2018-ZQN-74 to Ying-Biao Chen
文摘BACKGROUND Central sensitization plays a pivotal role in the maintenance of chronic pain induced by chronic pancreatitis(CP).We hypothesized that the nucleus tractus solitarius(NTS),a primary central site that integrates pancreatic afferents apart from the thoracic spinal dorsal horn,plays a key role in the pathogenesis of visceral hypersensitivity in a rat model of CP.AIM To investigate the role of the NTS in the visceral hypersensitivity induced by chronic pancreatitis.METHODS CP was induced by the intraductal injection of trinitrobenzene sulfonic acid(TNBS)in rats.Pancreatic hyperalgesia was assessed by referred somatic pain via von Frey filament assay.Neural activation of the NTS was indicated by immunohistochemical staining for Fos.Basic synaptic transmission within the NTS was assessed by electrophysiological recordings.Expression of vesicular glutamate transporters(VGluTs),N-methyl-D-aspartate receptor subtype 2B(NR2B),andα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subtype 1(GluR1)was analyzed by immunoblotting.Membrane insertion of NR2B and GluR1 was evaluated by electron microscopy.The regulatory role of the NTS in visceral hypersensitivity was detected via pharmacological approach and chemogenetics in CP rats.RESULTS TNBS treatment significantly increased the number of Fos-expressing neurons within the caudal NTS.The excitatory synaptic transmission was substantially potentiated within the caudal NTS in CP rats(frequency:5.87±1.12 Hz in CP rats vs 2.55±0.44 Hz in sham rats,P<0.01;amplitude:19.60±1.39 pA in CP rats vs 14.71±1.07 pA in sham rats;P<0.01).CP rats showed upregulated expression of VGluT2,and increased phosphorylation and postsynaptic trafficking of NR2B and GluR1 within the caudal NTS.Blocking excitatory synaptic transmission via the AMPAR antagonist CNQX and the NMDAR antagonist AP-5 microinjection reversed visceral hypersensitivity in CP rats(abdominal withdraw threshold:7.00±1.02 g in CNQX group,8.00±0.81 g in AP-5 group and 1.10±0.27 g in saline group,P<0.001).Inhibiting the excitability of NTS neurons via chemogenetics also significantly attenuated pancreatic hyperalgesia(abdominal withdraw threshold:13.67±2.55 g in Gi group,2.00±1.37 g in Gq group,and 2.36±0.67 g in mCherry group,P<0.01).CONCLUSION Our findings suggest that enhanced excitatory transmission within the caudal NTS contributes to pancreatic pain and emphasize the NTS as a pivotal hub for the processing of pancreatic afferents,which provide novel insights into the central sensitization of painful CP.
基金National Natural Science Foundation of China (No. 30470562).
文摘Objective Aims to delineate the distribution profile of three isoforms of vesicular glutamate transporter (VGluT), viz. VGluT1-3, and their cellular localization within vestibular nuclear complex (VNC). Methods Brain sections from normal Sprague-Dawley rats were processed immunohistochemically for VGluT detection, employing avidinbiotinylated peroxidase complex method with 3-3'-diaminobenzidine (DAB) as chromogen. Results The whole VNC expressed all of the three transporters that were observed to be localized to the fiber endings. Compared with VGluT1 and VGluT3, VGluT2 demonstrated a relatively homogeneous distribution, with much higher density in VNC. VGluT3 displayed the highest density in lateral vestibular nucleus and group X, contrasting with the sparse immunostained puncta within vestibular medial and inferior nuclei. Conclusion Glutamtatergic pathways participate in the processing of vestibular signals within VNC mainly through the re-uptake of glutamate into synaptic vesicles by VGluT1 and 2, whereas VGluT3 may play a similar role mainly in areas other than medial and inferior nuclei of VNC.
基金Supported by the National Key R&D Program of China,Precision Medicine Program-Cohort Study on Nervous System Diseases,No.2017YFC0907702。
文摘The pathogenesis of temporal lobe epilepsy(TLE)was originally considered to be acquired.However,some reports showed that TLE was clustered in some families,indicating a genetic etiology.With the popularity of genetic testing technology,eleven different types of familial TLE(FTLE),including ETL1-ETL11,have been reported,of which ETL9-ETL11 had not yet been included in the OMIM database.These types of FTLE were caused by different genes/Loci and had distinct characteristics.ETL1,ETL7 and ETL10 were characterized by auditory,visual and aphasia seizures,leading to the diagnosis of familial lateral TLE.ETL2,ETL3 and ETL6 showed prominent autonomic symptom and automatism with or without hippocampal abnormalities,indicating a mesial temporal origin.Febrile seizures were common in FTLEs such as ETL2,ETL5,ETL6 and ETL11.ETL4 was diagnosed as occipitotemporal lobe epilepsy with a high incidence of migraine and visual aura.Considering the diversity and complexity of the symptoms of TLE,neurologists enquiring about the family history of epilepsy should ask whether the relatives of the proband had experienced unnoticeable seizures and whether there is a family history of other neurological diseases carefully.Most FTLE patients had a good prognosis with or without anti-seizure medication treatment,with the exception of patients with heterozygous mutations of the CPA6 gene.The pathogenic mechanism was diverse among these genes and spans disturbances of neuron development,differentiation and synaptic signaling.In this article,we describe the research progress on eleven different types of FTLE.The precise molecular typing of FTLE would facilitate the diagnosis and treatment of FTLE and genetic counseling for this disorder.
基金Supported by Grants from the National Natural Science Foundation of China,No.30971123 and No.81371239
文摘AIM:To investigate the distribution and neurochemical phenotype of endomorphin-2(EM-2)-containing neurons in the submucosal plexus of the rat colon.METHODS:The mid-colons between the right and left flexures were removed from rats,and transferred into Kreb's solution. For whole-mount preparations,the mucosal,outer longitudinal muscle and inner circularmuscle layers of the tissues were separated from the submucosal layer attached to the submucosal plexus. The whole-mount preparations from each rat mid-colon were mounted onto seven gelatin-coated glass slides,and processed for immunofluorescence histochemical double-staining of EM-2 with calcitonin gene-related peptide(CGRP),choline acetyltransferase(Ch AT),nitric oxide synthetase(NOS),neuron-specific enolase(NSE),substance P(SP) and vasoactive intestinal peptide(VIP). After staining,all the fluorescence-labeled sections were observed with a confocal laser scanning microscope. To estimate the extent of the co-localization of EM-2 with CGRP,Ch AT,NOS,NSE,SP and VIP,ganglia,which have a clear boundary and neuronal cell outline,were randomly selected from each specimen for this analysis. RESULTS:In the submucosal plexus of the mid-colon,many EM-2-immunoreactive(IR) and NSE-IR neuronal cell bodies were found in the submucosal plexus of the rat mid-colon. Approximately 6 ± 4.2 EM-2-IR neurons aggregated within each ganglion and a few EM-2-IR neurons were also found outside the ganglia. The EM-2-IR neurons were also immunopositive for Ch AT,SP,VIP or NOS. EM-2-IR nerve fibers coursed near Ch AT-IR neurons,and some of these fibers were even distributed around Ch AT-IR neuronal cell bodies. Some EM-2-IR neuronal cell bodies were surrounded by SP-IR nerve fibers,but many long processes connecting adjacent ganglia were negative for EM-2 immunostaining. Long VIP-IR processes with many branches coursed through the ganglia and surrounded the EM-2-IR neurons. The percentages of the EM-2-IR neurons that were also positive for Ch AT,SP,VIP or NOS were approximately 91% ± 2.6%,36% ± 2.4%,44% ± 2.5% and 44% ± 4.7%,respectively,but EM-2 did not co-localize with CGRP. CONCLUSION:EM-2-IR neurons are present in the submucosal plexus of the rat colon and express distinct neurochemical markers.
基金National Natural Science Foundation of China Key Project 81130024National Natural Science Foundation of ChinaResearch Grants Council of Hong Kong Joint Research Scheme 8141101084
基金the National Natural Science Foundation of China (30470556)the Program for New Century Excellent Talents in University
文摘GABAergic neurons are the major inhibitory interneurons that powerfully control the function of spinal neuronal networks.In recent years,tremendous progresses have been made in understanding the transcriptional control of GABAergic neuron development in the dorsal spinal cord.New experimental approaches provide a relatively high throughput way to study the molecular regulation of subgroup fate determination.Our understanding of the molecular mechanisms on GABAergic neuron development in the dorsal spinal cord is rapidly expanding.Recent studies have defined several transcription factors that play essential roles in GABAergic neuron development in the spinal dorsal horn.Here,we review results of very recent analyses of the mechanisms that specify the GABAergic neuron development in the dorsal spinal cord,especially the progresses in the homeodomain(HD) and basic-helix-loop-helix(bHLH) containing transcription factors.
文摘Ventral tegmental area(VTA),which is well-documented as a modulatory center of reward and addiction,has been demonstrated to participate in pain processing.In addition,insula cortex(IC)has also been proved to be related with maintenance of neuropathic pain.In the present study,in order to clarify whether there exist dopaminergic projections from the VTA to the IC,retrograde and anterograde tracing methods combined with immunofluorescent histochemical staining were applied.The results revealed that almost all VTA-IC-projecting neurons originated from the VTA were dopaminergic neurons,with smaller amount of GABAergic neurons sending projection fiberss to the IC.
文摘Ventral lateral periaqueductal gray(vIPAG)is an essential transmit node in descending transmission pathway.However,whether neurons expressing different receptors in vIPAG paly distinct roles in nociception and pruriception remains elusive.To evaluate the possible effects of different neuroactive substances in vlPAG,cannula was implanted in the right side of the vIPAG.In the present study,a-amino 3-hydroxy-5-methyl-4-isoxazole-propionic acid(AMPA)receptor antagonist CNQX,N-methyl-D-aspartic acid(NMDA)receptor antagonist AP-5,Y-aminobutyric acid A(GABAs)receptor antagonist picrotoxin(PTX),μ-opioid receptor antagonist CTOP and calcitonin gene-related peptide(CGRP)antagonist CGRP8-37 were utilized.
文摘Central sensitization plays a pivotal role in the maintenance of chronic pain induced byvisceral diseases,including chronic pancreatitis(CP),but cortical modulation of painful CP remains elusive.This study was designed to examine the role of anterior insular cortex(aIC)in the pathogenesis of visceral hypersensitivity in a rat model of CP.CP was induced by intraductal administration of trinitrobenzene sulfonic acid(TNBS).Visceral hypersensitivity and anxiety were assessed by von Frey filament examination and open field test,respectively.Two weeks after surgery,neural activation within aIC was tested by both examining Fos expression and electrophysiological recordings.Expressions of VGluT1,NMDAR subunit NR2B and AMPAR subunit GluR1 were analyzed by immunoblottings.The regulatory roles of aIC in visceral hypersensitivity and pain-related anxiety were detected via pharmacological approach and chemogenetic test in CP rats.
文摘Central sensitizationis critical for chronic pain sensation induced by chronic pancreatitis(CP).We hypothesized that the nucleus tractus solitarius(NTS),a primary central site that integrates pancreatic afferents apart from the thoracic spinal dorsal horn,plays a key role in the pathogenesis of visceral hypersensitivity in a rat model of CP.In order to investigate the role of the NTS in the visceral hypersensitivity induced by chronic pancreatitis,CP was induced by the intraductal injection of trinitrobenzene sulfonic acid(TNBS)in rats.Pancreatic hyperalgesia was assessed by referred somatic pain via von Frey filament assay.Neural activation of the NTS was indicated by Fos-immunohistochemical staining.
文摘Diabetic mechanical allodynia(DMA)remains no effective treatment currently.TRPV4 is involved in mechanical sensation of varying etiologies,but expression feature and the whether it contributes to the DMA are so far unclear.