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Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

Neural Regeneration Research 2025年第7期20卷 1981-1988页

作者： Shan Ping Yu Emily Choi Michael QJiang Ling Wei Department of Anesthesiology Emory University School of MedicineAtlantaGAUSA center for Visual and Neurocognitive Rehabilitation Atlanta Veterans Affairs Medical CenterDecaturGAUSA

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same *** comorbidity of the two neurological disorders represents a grave health threat to older *** review presents a brief background of the development of novel concepts and their clinical *** activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal *** ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic *** Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute ***,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death *** on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic *** N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic *** stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time *** is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related

关键词： Ca^(2+)hypothesis cognitive deficits hyperactivity late-onset Alzheimer's disease neurodegeneration N-methyl-D-aspartate receptors N-methyl-D-aspartate receptor subunits pathogenesis preventive treatment

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A novel method for clustering cellular data to improve classification

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Neural Regeneration Research 2025年第9期20卷 2697-2705页

作者： Diek W.Wheeler Giorgio A.Ascoli center for Neural Informatics Structures&PlasticityKrasnow Institute for Advanced Study Bioengineering Department Volgenau School of Engineering George Mason University FairfaxVAUSA

Many fields,such as neuroscience,are experiencing the vast prolife ration of cellular data,underscoring the need fo r organizing and interpreting large datasets.A popular approach partitions data into manageable subsets via hierarchical clustering,but objective methods to determine the appropriate classification granularity are *** recently introduced a technique to systematically identify when to stop subdividing clusters based on the fundamental principle that cells must differ more between than within *** we present the corresponding protocol to classify cellular datasets by combining datadriven unsupervised hierarchical clustering with statistical *** general-purpose functions are applicable to any cellular dataset that can be organized as two-dimensional matrices of numerical values,including molecula r,physiological,and anatomical *** demonstrate the protocol using cellular data from the Janelia MouseLight project to chara cterize morphological aspects of neurons.

关键词： cellular data clustering dendrogram data classification Levene's one-tailed statistical test unsupervised hierarchical clustering

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Multisensory mechanisms of gait and balance in Parkinson’s disease:an integrative review

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Neural Regeneration Research 2025年第1期20卷 82-92页

作者： Stiven Roytman Rebecca Paalanen Giulia Carli Uros Marusic Prabesh Kanel Teus van Laar Nico I.Bohnen Department of Radiology University of MichiganAnn ArborMIUSA Department of Neurology University of MichiganAnn ArborMIUSA Morris K.Udall center of Excellence for Parkinson’s Disease Research University of MichiganAnn ArborMIUSA Institute for Kinesiology Research Science and Research Centre KoperKoperSlovenia Department of Health Sciences Alma Mater Europaea–ECMMariborSlovenia Parkinson’s Foundation Research center of Excellence University of MichiganAnn ArborMIUSA Department of Neurology University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands Neurology Service and GRECC VA Ann Arbor Healthcare SystemAnn ArborMIUSA

Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging *** and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous *** effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory *** mechanisms which underpin the integration of these multisensory signals are the principal topic of the present *** multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older *** emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and *** the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s *** also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older ***,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.

关键词： aging balance encephalography functional magnetic resonance imaging gait multisensory integration Parkinson’s disease positron emission tomography somatosensory vestibular visual

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Absence of high amplitude propagating contractions in subjects with chronic spinal cord injury

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World Journal of Gastroenterology 2010年第43期16卷 5435-5439页

作者： Hanumantha R Ancha Noel R Fajardo William A Bauman Alan S Rosman Marinella Galea Graham Creasey Mark A Korsten Rehabilitation Research and Development center of Excellence for medical Consequences of Spinal Cord Injury James J. Peters VA Medical Center medical Service James J. Peters VA Medical Center Department of Medicine Mount Sinai School of Medicine Department of Rehabilitation Medicine Mount Sinai School of Medicine Spinal Cord Injury Service James J. Peters VA Medical Center Spinal Cord Injury Service VA Medical Center

AIM: To investigate the presence or absence of high amplitude propagating contractions (HAPC), as well as the other measures of colonic motility, in persons with spinal cord injury (SCI). METHODS: Prolonged colonic ambulatory manometric studies were performed on 14 male volunteers: 8 with SCI (mean age, 59 ± 13 years; mean duration of injury, 13 ± 4 years) and 6 healthy able-bodied controls (mean age, 57 ± 10 years). A solid-state manometry catheter was endoscopically clipped to the splenic flexure. Recording was performed for > 24 h after manometric catheter placement. RESULTS: HAPC were absent in individuals with SCI during pre-sleep, sleep, and post-sleep phases. HAPC were significantly increased after awakening in non-SCI controls (0.8 ± 0.2 HAPC/h vs 10.5 ± 2.0 HAPC/h, P < 0.005). The motility index was lower in those with SCI than in controls preand post-sleep (SCI vs non-SCI: Pre-sleep, 2.4 ± 0.4 vs 8.8 ± 1.9, P < 0.01; Post-sleep, 4.3 ± 0.8 vs 16.5 ± 4.5, P < 0.05). However, a sleepinduced depression of colonic motility was observed in both the SCI and non-SCI groups (Pre-sleep vs Sleep, non-SCI: 8.8 ± 1.9 vs 2.1 ± 0.9, P < 0.002; SCI: 2.4 ± 0.4 vs 0.2 ± 0.03, P < 0.001), with the motility index of those with SCI during sleep not significantly different than that of the controls. CONCLUSION: HAPC were not observed in individuals with SCI preor post-sleep. A sleep-induced depression in general colonic motility was evident in SCI and control subjects.

关键词： Spinal cord injury Neurogenic bowel Bowel motility High amplitude propagating contractions Motility index

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Skeletal muscle stiffness as measured by magnetic resonance elastography after chronic spinal cord injury:a cross-sectional pilot study

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Neural Regeneration Research 2021年第12期16卷 2486-2493页

作者： Mina P.Ghatas M.Rehan Khan Ashraf S.Gorgey Department of Spinal Cord Injury and Disorders Hunter Holmes McGuire VA Medical CenterRichmondVAUSA Department of Radiology Hunter Holmes McGuire VA Medical CenterRichmondVAUSA Department of Physical Medicine and Rehabilitation Virginia Commonwealth UniversityRichmondVAUSA

Skeletal muscle stiffness is altered after spinal cord injury(SCI).Assessing muscle stiffness is essential for rehabilitation and pharmaceutical interventions design after *** study used magnetic resonance elastography to assess the changes in stiffness after chronic SCI compared to matched able-bodied controls and determine its association with muscle size,spasticity,and peak torque in persons with *** studies examined the association between muscle stiffness and spasticity,however,we are unaware of other studies that examined the effects of muscle composition on stiffness after *** participants(one female)with chronic SCI and eight(one female)matched able-bodied controls participated in this cross-sectional *** resonance elastography was utilized to monitor stiffness derived from shear waves *** Ashworth scale was used to evaluate spasticity scores in a blinded *** isometric and isokinetic torques were measured using a biodex *** values were non-significantly lower(12.5%;P=0.3)in the SCI group compared to able-bodied ***,stiffness was positively related to vastus lateralis whole muscle cross-sectional area(CSA)(r2=0.64,Pvastus lateralis absolute muscle CSA after accounting for intramuscular fat(r2=0.78,P<0.0007).Stiffness was also positively correlated to both isometric(r2=0.55-0.57,P<0.05)and isokinetic peak(r2=0.46-0.48,P<0.05)*** results suggest that larger clinical trial is warranted to confirm the preliminary findings that muscle stiffness is altered after SCI compared to healthy *** appeared to be influenced by infiltration of intramuscular fat and modestly by the spasticity of the paralyzed *** preliminary data indicated that the relationship between muscle stiffness and peak torque is not altered with changing the frequency of pulses or angular *** study procedures were approved by the Institutional Review Board at the

关键词： chronic spinal cord injury isometric and isokinetic torques magnetic resonance elastography muscle size rehabilitation shear modulus spasticity stiffness

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Genotypic characteristics of resistant tumors to pre-operative ionizing radiation in rectal cancer

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World Journal of Gastrointestinal Oncology 2014年第7期6卷 194-210页

作者： Zeeshan Ramzan Ammar B Nassri Sergio Huerta va North Texas Healthcare System-Dallas va medical center University of Texas Southwestern Medical Center Dallas TX 75216 United States

Due to a wide range of clinical response in patients un-dergoing neo-adjuvant chemoradiation for rectal cancer it is essential to understand molecular factors that lead to the broad response observed in patients receiving the same form of *** extensive research in this field,the exact mechanisms still remain *** raging from DNA-repair to specific molecules lead-ing to cell survival as well as resistance to apoptosis have been ***,or in combination,there is no single pathway that has become clinically applicable to *** the following review,we describe the current status of various pathways that might lead to resistance to the therapeutic applications of ionizing radiation in rectal cancer.

关键词： Ionizing radiation DNA double-strand break Non-homologous end-joining pathway DNA-PKcs Ku proteins Complete pathological response Radiation therapy Apoptosis Angiogenesis

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Metallic biliary stents for malignant obstructive jaundice:a review

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World Journal of Gastroenterology 2000年第5期6卷 643-646页

作者： Richard A.Kozarek Section of Gastroenterology Virginia Mason Medical CenterSeattleWAUSA MD

Affecting 8-10 patients per 100000population,pancreatic cancer is the primary causeof malignant obstructive jaundice and is thepresenting feature in over three quarters of ***,using modern imagingtechniques,such as endoscopic ultrasound orpancreatic protocol computed tomography withvascular reconstruction,80%-90% proveunrescctable for ***,this jaundicewas treated surgically with biliary ***

关键词： pancreatic neoplasms bile duct neoplasms cholangiopancreatography endoscopic retrograde cholestasis stents

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Targeted therapy in gastroesophageal cancers:past,present and future

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Gastroenterology Report 2015年第4期3卷 316-329,I0002页

作者： Janghee Woo Stacey A.Cohen Jonathan E.Grim Clinical Research Division Fred Hutchinson Cancer Research CenterSeattleWAUSA Division of medical Oncology University of WashingtonSeattleWAUSA Hospital and Specialty Medicine VA Puget Sound Health Care SystemSeattleWAUSA

Gastroesophageal cancer is a significant global problem that frequently presents at an incurable stage and has very poor survival with standard chemotherapy *** review will examine the epidemiology and molecular biology of gastroesophageal cancer and will focus on the key deregulated signaling pathways that have been targeted in the clinic.A comprehensive overview of clinical data highlighting successes and failures with targeted agents will be *** notably,HER2-targeted therapy with the monoclonal antibody trastuzumab has proven beneficial in first-line therapy and has been incorporated into standard *** the VEGF pathway has also proven beneficial,and the VEGFR-targeted monoclonal antibody ramucirumab is now approved for second-line *** contrast to these positive results,agents targeting the EGFR and MET pathways have been evaluated extensively in gastroesophageal cancer but have repeatedly failed to show *** increased understanding of the molecular predictors of response to targeted therapies is sorely *** the future,improved molecular pathology approaches should subdivide this heterogeneous disease entity to allow individualization of cancer therapy based on integrated and global identification of deregulated signaling *** patient selection,rational combinations of targeted therapies and incorporation of emerging immunotherapeutic approaches should further improve the treatment of this deadly disease.

关键词： esophageal cancer gastric cancer targeted therapy molecular oncology

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Androgens and prostate disease

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Asian Journal of Andrology 2014年第2期16卷 248-255,I0009页

作者： Lori A Cooper Stephanie T Page Departments of Medicine Division of Endocrinology and Metabolism University of Washington Seattle University of Washington and Harborview medical center Seattle Washington USA.

A growing body of literature has established the anabolic benefits of testosterone （T） therapy in hypogonadal men. However, there remains a paucity of data regarding the risks of exogenous androgen use in older men and the potential for adverse effects on the prostate gland. Whether T therapy in older, hypogonadal men might worsen lower urinary tract symptoms or exacerbate, unmask, or even incite prostate cancer development has tempered enthusiasm for T therapy, while known prostatic disease has served as a relative contraindication to T therapy. Androgens are necessary for the development and maintenance of the prostate gland. However, epidemiologic studies do not consistently find a positive relationship between endogenous serum androgen concentrations and the risk of prostate disease. Recent data demonstrate that 5α-reductase inhibitors decrease the risk of low-grade prostate cancer, suggesting that modifying androgen metabolism may have beneficial effects on prostate health, yet similar reductions in high-grade disease have not been observed, thereby questioning the true clinical benefits of these agents for chemoprevention. Knowing how to best investigate the relationship between androgens and the development of prostate disease given the lack of large, randomized trials is difficult. Accumulating data challenges the assumption that alterations in serum androgens have parallel effects within the prostate hormonal environment or change androgen-regulated processes within the gland. Long-term intervention studies are needed to truly ascertain the effects of androgen manipulation on prostate tissue and disease risk. However, available data do not support the notion that restoring serum androgens to normal physiologic ranges drives prostate disease.

关键词： androgens male hypogonadism prostate testosterone

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One year experience with computer-assisted propofol sedation for colonoscopy

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World Journal of Gastroenterology 2017年第16期23卷 2964-2971页

作者： Otto S Lin Danielle La Selva Richard A Kozarek Deborah Tombs Wade Weigel Ryan Beecher Johannes Koch Susan Mc Cormick Michael Chiorean Fred Drennan Michael Gluck Nanda Venu Michael Larsen Andrew Ross Digestive Disease Institute Virginia Mason Medical CenterSeattleWA 98101United States Department of Anesthesia Virginia Mason Medical CenterSeattleWA 98101United States

AIM To report our one-year experience with computer assisted propofol sedation(CAPS) for colonoscopy as the first United States medical center to adopt CAPS technology for routine clinical *** Between September 2014 and August 2015, 2677 patients underwent elective outpatient colonoscopy with CAPS at our center. All colonoscopies were performed by 1 of 17 gastroenterologists certified in the use of the CAPS system, with the assistance of a specially trained nurse. Procedural success rates, polyp detection rates, procedure times and recovery times were recorded and compared against corresponding historical measuresfrom 2286 colonoscopies done with midazolam and fentanyl from September 2013 to August 2014. Adverse events in the CAPS group were *** The mean age of the CAPS cohort was 59.9 years(48.7% male); 31.3% were ASA?Ⅰ, 67.3% ASA Ⅱ and 1.4% ASA Ⅲ. 45.1% of the colonoscopies were for screening, 31.5% for surveillance, and 23.4% for symptoms. The mean propofol dose administered was 250.7 mg(range 16-1470 mg), with a mean fentanyl dose of 34.1 mcg(0-100 mcg). The colonoscopy completion and polyp detection rates were similar to that of historical measures. Recovery times were markedly shorter(31 min vs 45.6 min, P < 0.001). In CAPS patients, there were 20(0.7%) cases of mild desaturation(< 90%) treated with a chin lift and reduction or temporary discontinuation of the propofol infusion, 21(0.8%) cases of asymptomatic hypotension(< 90 systolic blood pressure) treated with a reduction in the propofol rate, 4(0.1%) cases of marked agitation or discomfort due to undersedation, and 2 cases of pronounced transient desaturation requiring brief(< 1 min) mask ventilation. There were no sedation-related serious adverse events such as emergent intubation, unanticipated hospitalization or permanent injury. CONCLUSION CAPS appears to be a safe, effective and efficient means of providing moderate sedation for colonoscopy in relatively healthy patients. Recovery

关键词： Colonoscopy Propofol Sedation Colon cancer screening Anesthesia

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