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Adenosine A_(2A)receptor blockade attenuates excitotoxicity in rat striatal medium spiny neurons during an ischemic-like insult

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Neural Regeneration Research 2024年第2期19卷 255-257页

作者： Elisabetta Coppi Federica Cherchi Alasdair J.Gibb department of neuroscience PsychologyDrug Research and Child HealthUniversity of FlorenceFlorenceItaly department of neuroscience Physiology and PharmacologyUniversity College LondonLondonUK

During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue ***,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membrane ion gradients,occurs in vivo or in vitro during an energy *** neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors,namely:A_(1),A_(2A),A_(2B),and A_(3).The A_(2A)receptor subtype is highly expressed in striatal medium spiny neurons,which are particularly susceptible to ischemic *** indicates that the A2Areceptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 *** recently added new knowledge to the mechanisms by which the adenosine A2Areceptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose *** demonstrated that the selective block of A2Areceptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+channel modulation and a presynaptic inhibition of glutamate release by the A2Areceptor *** present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2Areceptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.

关键词： adenosine A_(2A)receptors anoxic depolarization brain ischemia glutamate excitotoxicity medium spiny neurons oxygen and glucose deprivation

Premature axon-oligodendrocyte interaction contributes to stalling of experimental axon regeneration after injury to the white matter

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Neural Regeneration Research 2024年第3期19卷 469-470页

作者： Ephraim F.Trakhtenberg department of neuroscience University of Connecticut School of MedicineFarmingtonCTUSA

Studies from nearly 3 decades ago suggested that,in the central nervous system(CNS),myelination of axons by oligodendrocytes not only helps improve axonal conductivity but also stabilizes circuitry(Colello and Schwab,1994).Over the years,myelin sheaths produced by oligodendrocytes have been found to contain multiple molecules that are inhibitory to axonal growth(e.g.,MAG,NogoA,OMgp,Semaphorins)(Yiu and He,2006;Silver et al.,2014).After white matter injury in the adult CNS,myelin debris from damaged axons and dead oligodendrocytes accumulates in the forming glial scar and exposes these myelin-associated axon growth-inhibitory molecules to the injured axonal stumps,thereby contributing to the inhibition of axonal *** development,CNS axons reach their postsynaptic targets and stop growing before oligodendrocytes appear and myelinate them(Foran and Peterson,1992;Dangata et al.,1996).Therefore,myelin-associated axon growth-inhibitory molecules interacting with already grown axons during myelination were thought to block axons from promiscuous sprouting and miswiring,thereby stabilizing neural circuitry in the CNS(Colello and Schwab,1994).

关键词： thereby white injury

Beyond functional MRI signals:molecular and cellular modifiers of the functional connectome and cognition

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Neural Regeneration Research 2024年第5期19卷 937-938页

作者： Lorenzo Pini Alessandro Salvalaggio Maurizio Corbetta Padova neuroscience Center University of PadovaItaly Veneto Institute of Molecular Medicine VIMMPadovaItaly department of neuroscience University of PadovaItaly

Our brain is constantly *** at rest,the brain carries out essential functions such as maintenance of resting potentials,subthreshold synaptic activity,and spiking activity related to information *** resting activity can be assessed with several in vivo tools,such as resting-state functional magnetic resonance *** technique measures subtle changes in blood flow,volume,and oxygenation that occur over *** vascular in nature,resting-state functional magnetic resonance imaging is considered a reliable proxy of neural activity and several studies have shown that the brain is functionally divided into interacting neural networks called the“functional connectome”.

关键词： functional neural measures

Resilience conferred by APOE-R136S:a defense bestowed by nature to combat Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2024年第3期9卷 831-832页

作者： Bin Xiao Joshua Kuruvilla Eng-King Tan department of Neurology National Neuroscience InstituteSingaporeSingapore neuroscience Academic Clinical Program Duke-NUS Medical SchoolSingaporeSingapore neuroscience and Behavioural Disorders Program Duke-NUS Medical SchoolSingaporeSingapore

In two recent articles published in Nature neuroscience and Cell,Nelson et al.1 and Chen et al.2 have shown that a rare APOE3 Christchurch(APOE3Ch)variant,R136S,has protective effects on neurodegeneration in various Alzheimer’s disease(AD)model systems through attenuating tau pathology and regulating its related neuroimmune *** et *** Chen et *** provided evidence that identifying the pathophysiologic clues and potential molecular targets from a protective variant such as APOE R136S,can be an attractive viable approach to develop AD therapeutics.

关键词： protective al. Alzheimer

General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain

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Zoological Research 2024年第3期45卷 691-703页

作者： Wen-Xin Hang Yan-Chang Yang Yu-Han Hu Fu-Quan Fang Lang Wang Xing-Hua Qian Patrick M.McQuillan Hui Xiong Jian-Hang Leng Zhi-Yong Hu department of anesthesiology First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310003China department of Cell Biology Yale UniversityNew HavenCT 06520USA department of Neurology of the First Affiliated Hospital Interdisciplinary Institute of Neuroscience and TechnologySchool of Brain Science and Brain MedicineZhejiang University School of MedicineHangzhouZhejiang 310027China department of anesthesiology Jiaxing Maternity and Childcare Health HospitalJiaxingZhejiang 314009China department of anesthesiology Penn State Hershey Medical CentrePenn State College of MedicineHersheyPA 17033USA department of Central Laboratory Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang 310006China

General anesthetic agents can impact brain function through interactions with neurons and their effects on glial *** perform essential roles in the central nervous system,including myelin sheath formation,axonal metabolism,and neuroplasticity *** are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation,differentiation,and *** are increasingly interested in the effects of general anesthetic agents on *** agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways,but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and *** this review,we summarize the effects of general anesthetic agents on *** anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.

关键词： Oligodendrocytes General anesthetic agents Neurotoxicity Central nervous system Perioperative neurocognitive disorders

Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans:an overview of recent findings

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Neural Regeneration Research 2024年第9期19卷 1908-1918页

作者： Marcello Serra Nicola Simola Alexia E.Pollack Giulia Costa department of Biomedical Sciences Section of NeuroscienceUniversity of CagliariCagliariItaly department of Biology University of Massachusetts-BostonBostonMAUSA

Preclinical and clinical studies indicate that psychostimulants,in addition to having abuse potential,may elicit brain dysfunctions and/or neurotoxic *** toxicity induced by psychostimulants may pose serious health risks since the recreational use of these substances is on the rise among young people and *** present review provides an overview of recent research,conducted between 2018 and 2023,focusing on brain dysfunctions and neurotoxic effects elicited in experimental models and humans by amphetamine,cocaine,methamphetamine,3,4-methylenedioxymethamphetamine,methylphenidate,caffeine,and *** elucidation of factors and mechanisms that underlie psychostimulant-induced brain dysfunction and neurotoxicity is crucial for understanding the acute and enduring noxious brain effects that may occur in individuals who use psychostimulants for recreational and/or therapeutic purposes.

关键词： 3,4-methylenedioxymethamphetamine amphetamine caffeine cell cultures cocaine methamphetamine methylphenidate neurotoxicity nicotine

A perspective on age-related changes in cell environment and risk of neurodegenerative diseases

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Neural Regeneration Research 2024年第4期19卷 719-720页

作者： Alice Y.Liu department of Cell Biology and neuroscience Rutgers State University of New JerseyPiscatawayNJUSA

“Age-related neurodegenerative disease”underscores human age as the primary risk factor for disease development:Alzheimer’s,Parkinson’s,and Huntington’s disease(HD)as *** for the age-dependent delay in disease manifestation,in particular for autosomal dominant forms of the disease,and the underlying cause(s)of specific neuron dysfunction and death to manifest as memory loss,anxiety,depression,and agitation in disease subjects remain *** are interested in understanding age-related changes in cell environment that can modulate the structure,function,aggregation.

关键词： Huntington Alzheimer death

Neuron-to-astrocyte proteostatic stress signaling in response to tau pathology

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Neural Regeneration Research 2024年第3期19卷 505-506页

作者： Kevin Llewelyn Batenburg Wiep Scheper Amsterdam UMC location Vrije Universiteit Amsterdam Department of Human GeneticsAmsterdam Neuroscience-NeurodegenerationAmsterdamThe Netherlands department of Functional Genomics Center for Neurogenomics and Cognitive ResearchVrije Universiteit AmsterdamAmsterdam Neuroscience-NeurodegenerationAmsterdamThe Netherlands

Maintenance of protein homeostasis or“proteostasis”is essential for the functioning and viability of *** is in particular the case for cells like neurons that cannot self-renew and acquire unique functional properties during their *** proteostatic stress responses are in place to protect cells from damage in case of proteostatic *** integrated stress response(ISR)is one of the key proteostatic stress responses in the cell(Costa-Mattioli and Walter,2020).The ISR is the downstream convergence point for the four stress-induced eIF2αkinases(EIF2AK1-4)that control stress-regulated protein translation via phosphorylation of the translation factor eIF2α.ISR activation results in a transient reduction of global translation while it concomitantly enhances the translation of specific mRNAs,including that encoding the activating transcription factor 4(ATF4).Together,the translational control mediated by the ISR results in a temporary reduction of the overall protein load and the selectively increased expression of proteins that contribute to restoration of the proteostatic balance.

关键词： translation stress Together

Reduction of epinephrine in the lumbar spinal cord following repetitive blast-induced traumatic brain injury in rats

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Neural Regeneration Research 2024年第7期19卷 1548-1552页

作者： Shigeharu Tsuda Mustafa Golam Jiamei Hou Kevin K.W.Wang Floyd J.Thompson Prodip Bose Brain Rehabilitation Research Center Malcom Randall VA Medical CenterNorth Florida/South Georgia Veterans Health SystemGainesvilleFLUSA department of anesthesiology College of MedicineUniversity of FloridaGainesvilleFLUSA department of Emergency Medicine University of FloridaGainesvilleFLUSA department of neuroscience University of FloridaGainesvilleFLUSA department of Neurology University of FloridaGainesvilleFLUSA

Traumatic brain inju ry-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines,especially epinephrine,although few preclinical studies have examined the epinephrine level in the central nervous system after traumatic brain *** has been shown to regulate the activities of spinal motoneurons as well as increase the heart rate,blood pressure,and blood flow to the hindlimb ***,the purpose of the present study was to determine the impact of repeated blast-induced traumatic brain injury on the epinephrine levels in seve ral function-s pecific central nervous system regions in *** three repeated blast injuries at 3-day intervals,the hippocampus,motor cortex,locus coeruleus,vestibular nuclei,and lumbar spinal cord were harvested at post-injury day eight and processed for epinephrine assays using a high-sensitive electrochemical detector cou pled with high-performance liquid *** results showed that the epinephrine levels were significantly decreased in the lumbar spinal cord tissues of blast-induced traumatic brain injury animals compared to the levels detected in age-and sex-matched sham *** other function-specific central nervous system regions,although the epinephrine levels were slightly altered following blast-induced tra u matic brain injury,they were not statistically *** results suggest that blast injury-induced significant downregulation of epinephrine in the lumbar spinal cord could negatively impact the motor and cardiovascular *** is the first repo rt to show altered epinephrine levels in the spinal cord following repetitive mild blast-induced traumatic brain injury.

关键词： balance blood flow cardiovascular system central nervous system epinephrine ischemic damage lumbar spinal cord muscle tone repeated blast spasticity traumatic brain injury