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Music as medicine for traumatic brain injury:a perspective on future research directions

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Neural Regeneration Research 2024年第10期19卷 2105-2106页

作者： Anthony E.Kline Eleni H.Moschonas Corina O.Bondi Department of Physical Medicine&Rehabilitation University of PittsburghPittsburghPAUSA Safar center for Resuscitation Research University of PittsburghPittsburghPAUSA center for neuroscience University of PittsburghPittsburghPAUSA Department of Critical Care Medicine University of PittsburghPittsburghPAUSA center for the Neural Basis of Cognition University of PittsburghPittsburghPAUSA Department of Psychology University of PittsburghPittsburghPAUSA Department of Neurobiology University of PittsburghPittsburghPAUSA

Traumatic brain injury(TBI) impacts 69 million individuals globally each year and is a leading cause of death and disability(Dewan et al.,2019).The majority of moderate-to-severe TBI survivors endure long-lasting disturbances in motor,cognitive,and affect that negatively impacts their *** a plethora of research on pharmacological interventions for TBI has been conducted,none has translated to the clinic,thus advocating for the evaluation of nonpharmacological therapeutic approaches that may increase translational success.

关键词： injury traumatic

Fully flexible implantable neural probes for electrophysiology recording and controlled neurochemical modulation

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Microsystems & Nanoengineering 2024年第3期10卷 317-333页

作者： Mohammad Hassan Malekoshoaraie Bingchen Wu Daniela DKrahe Zabir Ahmed Stephen Pupa Vishal Jain Xinyan Tracy Cui Maysamreza Chamanzar Electrical and Computer Engineering Carnegie Mellon UniversityPittsburghPA 15213USA Bioengineering University of PittsburghPittsburghPA 15260USA center for Neural Basis of Cognition University of Pittsburgh and Carnegie Mellon UniversityPittburgh 15213USA McGowan Institute for Regenerative Medicine University of PittsburghPittsburgh 15219USA Carnegie Mellon neuroscience Institute Carnegie Mellon UniversityPittsburgh 15213USA

Targeted delivery of neurochemicals and biomolecules for neuromodulation of brain activity is a powerful technique that,in addition to electrical recording and stimulation,enables a more thorough investigation of neural circuit *** have designed a novel,flexible,implantable neural probe capable of controlled,localized chemical stimulation and electrophysiology *** neural probe was implemented using planar micromachining processes on Parylene C,a mechanically flexible,biocompatible *** probe shank features two large microelectrodes(chemical sites)for drug loading and sixteen small microelectrodes for electrophysiology recording to monitor neuronal response to drug *** reduce the impedance while keeping the size of the microelectrodes small,poly(3,4-ethylenedioxythiophene)(PEDOT)was electrochemically coated on recording *** addition,PEDOT doped with mesoporous sulfonated silica nanoparticles(SNPs)was used on chemical sites to achieve controlled,electrically-actuated drug loading and *** neurotransmitters,including glutamate(Glu)and gamma-aminobutyric acid(GABA),were incorporated into the SNPs and electrically triggered to release *** in vitro experiment was conducted to quantify the stimulated release profile by applying a sinusoidal voltage(0.5 V,2 Hz).The flexible neural probe was implanted in the barrel cortex of the wild-type Sprague Dawley *** expected,due to their excitatory and inhibitory effects,Glu and GABA release caused a significant increase and decrease in neural activity,respectively,which was recorded by the recording *** novel flexible neural probe technology,combining on-demand chemical release and high-resolution electrophysiology recording,is an important addition to the neuroscience toolset used to dissect neural circuitry and investigate neural network connectivity.

关键词： Parylene recording release

Cell replacement with stem cell-derived retinal ganglion cells from different protocols

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Neural Regeneration Research 2024年第4期19卷 807-810页

作者： Ziming Luo Kun-Che Chang Spencer center for Vision Research Byers Eye InstituteStanford University School of Medicine Department of Ophthalmology Louis J.Fox Center for Vision RestorationUniversity of Pittsburgh School of Medicine Department of Neurobiology Center of NeuroscienceUniversity of Pittsburgh School of Medicine

Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness *** is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after *** stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative *** this review,we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture,including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation ***,we discuss using 3D retinal organoids for retinal ganglion cell transplantation,comparing cell suspensions and *** review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation,with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.

关键词： cell clumps cell suspension cell transplantation differentiation direct-induced protocol glaucoma optic neuropathy regenerative medicine retinal ganglion cell retinal organoids stem cells

Movement Trend Alterations in the Periaqueductal Gray(PAG)-Employed Ratbot Navigation Are Correlated with Stimulation Parameters

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Journal of Bionic Engineering 2024年第2期21卷 866-876页

作者： Sina Khajei Abed Khorasani Mohammad Reza Afarinesh Vahid Sheibani neuroscience Research center Institute of NeuropharmacologyKerman University of Medical SciencesKerman***Iran Cognitive neuroscience Research center Institute of NeuropharmacologyKerman University of Medical SciencesKerman***Iran

In previous studies,Periaqueductal Gray(PAG)stimulation was used to stop ratbots from *** to the homology between the PAG and the intercollicular nucleus,which has been used for forward movement in birds,we investigated the possibility of PAG application to induce forward locomotion for the first *** a corridor maze,the traveled distances via PAG electrical stimulation were examined in nine Wistar male rats during three sessions.A custom-designed stimulator was developed to apply the *** results showed reductions in responses to stimulation over ***,the traveled distances had negative slopes during the consecutive trials(in 8 out of the 9 rats),and the slope mean was significantly different from *** was a strong correlation between the stimulation parameters(electric Charge per Phase(CPP)and the Number of Pulses(NP))and the observed *** negative Movement Slopes(MS)were highly correlated with the CPP and the NP,as the Pearson's linear correlation coefficients were−0.87 and−0.79,*** MS-CPP coefficients of determination(R-squared)were also between 0.76 and *** addition,the MS-NP coefficients of determination were between 0.63 and ***,it is concluded that the electrical stimulation parameters influence the behavioral outcomes ***,the PAG area may be considered a suitable candidate for forward locomotion control in the future if the area is harnessed effectively to prevent undesirable chaotic behaviors.

关键词： Periaqueductal Gray(PAG) Navigation Ratbot Animal-robot Forward locomotion Movement slope

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

Translating Pathological Brain Activity Primers in Parkinson’s Disease Research

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Research 2024年第1期2023卷 735-752页

作者： Daniela Mirzac Svenja L.Kreis Heiko J.Luhmann Gabriel Gonzalez-Escamilla Sergiu Groppa Movement Disorders and Neurostimulation Department of NeurologyFocus Program Translational NeuroscienceRhine Main Neuroscience NetworkUniversity Medical Center of the Johannes Gutenberg University Mainz55131 MainzGermany Institute of Physiology University Medical Center of the Johannes Gutenberg University Mainz55131 MainzGermany

Translational experimental approaches that help us better trace Parkinson’s disease(PD)pathophysiological mechanisms leading to new therapeutic targets are urgently *** this article,we review recent experimental and clinical studies addressing abnormal neuronal activity and pathological network oscillations,as well as their underlying mechanisms and *** aim is to enhance our knowledge about the progression of Parkinson's disease pathology and the timing of its symptom’s ***,we present mechanistic insights relevant for the generation of aberrant oscillatory activity within the cortico-basal ganglia *** summarize recent achievements extrapolated from available PD animal models,discuss their advantages and limitations,debate on their differential applicability,and suggest approaches for transferring knowledge on disease pathology into future research and clinical applications.

关键词： clinical knowledge insight

TRP Channels in Stroke

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neuroscience Bulletin 2024年第8期40卷 1141-1159页

作者： Pengyu Zong Cindy XLi Jianlin Feng Mara Cicchetti Lixia Yue Department of Cell Biology Calhoun Cardiology CenterSchool of Medicine(UConn Health)University of ConnecticutFarmingtonCT 06030USA Institute for the Brain and Cognitive Sciences University of Connecticut337 Mansfield RoadUnit 1272StorrsCT 06269USA Present Address:Department of neuroscience University of Pittsburgh4200 Fifth AvePittsburghPA 15260USA

Ischemic stroke is a devastating disease that affects millions of patients ***,there are no effective medications for mitigating brain injury after ischemic *** channels are evolutionally ancient biosensors that detect external stimuli as well as tissue or cellular *** date,many members of the TRP superfamily have been reported to contribute to ischemic brain injury,including the TRPC subfamily(1,3,4,5,6,7),TRPV subfamily(1,2,3,4)and TRPM subfamily(2,4,7).These TRP channels share structural similarities but have distinct channel functions and *** activation during ischemic stroke can be beneficial,detrimental,or even *** this review,we focus on discussing the interesting features of stroke-related TRP channels and summarizing the underlying cellular and molecular mechanisms responsible for their involvement in ischemic brain injury.

关键词： Stroke TRP channels-Neuronal death Immune cell infiltration Blood-brain barrier Glial activation

Sulfation of chondroitin and bile acids converges to antagonize Wnt/β-catenin signaling and inhibit APC deficiency-induced gut tumorigenesis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1241-1256页

作者： Pengfei Xu Yue Xi Jong-Won Kim Junjie Zhu Min Zhang Meishu Xu Songrong Ren Da Yang Xiaochao Ma Wen Xie center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261USA Department of Hepatobiliary and Pancreatic Surgery Zhongnan Hospital of Wuhan UniversitySchool of Pharmaceutical SciencesWuhan UniversityWuhan 430071China Department of Pharmacology&Chemical Biology University of PittsburghPittsburghPA 15261USA

Sulfation is a crucial and prevalent conjugation reaction involved in cellular processes and mammalian physiology.3’-Phosphoadenosine 5’-phosphosulfate(PAPS)synthase 2(PAPSS2)is the primary enzyme to generate the universal sulfonate donor *** involvement of PAPSS2-mediated sulfation in adenomatous polyposis coli(APC)mutation-promoted colonic carcinogenesis has not been ***,we showed that the expression of PAPSS2 was decreased in human colon tumors along with cancer stages,and the lower expression of PAPSS2 was correlated with poor prognosis in advanced colon *** epithelial-specific heterozygous Apc deficient and Papss2-knockout(Apc^(Δgut-Het)Papss2^(Δgut))mice were created,and the phenotypes were compared to the spontaneous intestinal tumorigenesis of Apc^(Δgut-Het)***^(Δgut-Het)Papss2^(Δgutmice) were more sensitive to gut tumorigenesis,which was mechanistically accounted for by the activation of Wnt/β-catenin signaling pathway due to the suppression of chondroitin sulfation and inhibition of the farnesoid X receptor(FXR)-transducin-like enhancer of split 3(TLE3)gene regulatory *** sulfate supplementation in Apc^(Δgut-Het)Papss2^(Δgutmice) alleviated intestinal *** summary,we have uncovered the protective role of PAPSS2-mediated chondroitin sulfation and bile acids-FXR-TLE3 activation in the prevention of gut carcinogenesis via the antagonization of Wnt/β-catenin *** sulfate may be explored as a therapeutic agent for Papss2 deficiency-associated colonic carcinogenesis.

关键词： Colon cancer APC Wnt/b-catenin PAPSS2 Chondroitin sulfate Sulfation Bile acids FXR

Blood-brain barrier pathology in cerebral small vessel disease

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Neural Regeneration Research 2024年第6期19卷 1233-1240页

作者： Ruxue Jia Gemma Solé-Guardia Amanda J.Kiliaan Department of Medical Imaging AnatomyRadboud University Medical CenterDonders Institute for BrainCognition&BehaviorCenter for Medical NeurosciencePreclinical Imaging Center PRIMERadboud Alzheimer CenterNijmegenthe Netherlands

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the *** at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of *** signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease *** pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier ***,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel ***,the purpose of this review is to provide a new foundation in the study of small vessel disease ***,we discuss the main structural domains and functions of the blood-brain ***,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel ***,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

关键词： blood-brain barrier dysfunction cerebral blood flow cerebral hypoperfusion endothelial dysfunction hypertension inflammation magnetic resonance imaging neurovascular unit oxidative stress small vessel disease tight junctions transcytosis