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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander J.P.Goldschmidt Damien D.Pearse w.dalton dietrich Allan D.Levi James D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Clinical significance and potential translation of neural regeneration and functional recovery in monkeys after spinal cord injury

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Science China(Life Sciences) 2018年第10期61卷 1291-1292页

作者： w.dalton dietrich Leonard M.Miller School of Medicine University of MiamiMiami FL 33136 USA

The recent manuscript by Dr. Rao and colleagues (Rao et al.,2018) reports on a new combinational strategy that significantly promotes neural regeneration and improves motor and sensory function in nonhuman primates after severe spinal cord injury (SCI). This acute reparative strategy that included the insertion of neurotrophin 3-loaded chitosan biodegradable material into a 1-cm gap of the hemisectioned spinal cord had previously been tested in rodent models of SCI. In addition to showing that this reparative approach

关键词：绳索新生神经翻译猴子临床最小公倍数感觉功能

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Does being female provide a neuroprotective advantage following spinal cord injury?

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Neural Regeneration Research 2015年第10期10卷 1533-1536页

作者： Jeffrey P.Datto Jackie Yang w.dalton dietrich Damien D.Pearse The Miami Project to Cure Paralysis University of Miami Miller School of Medicine The Department of Neurological Surgery University of Miami Miller School of Medicine The Department of Neurology University of Miami Miller School of Medicine The Department of Cell Biology University of Miami Miller School of Medicine The Neuroscience Program University of Miami Miller School of Medicine The Interdisciplinary Stem Cell Institute University of Miami Miller School of Medicine

It has been controversial whether gender has any effect on recovery following spinal cord injury（SCI）. Past experimental and clinical research aimed at addressing this subject has led to constrasting findings on whether females hold any advantage in locomotor recovery. Additionally, for studies supporting the notion of a female gender related advantage, a definite cause has not been explained. In a recent study, using large sample sizes for comparative male and female spinal cord injury cohorts, we reported that a significant gender advantage favoring females existed in both tissue preservation and functional recovery after taking into consideration discrepancies in age and weight of the animals across sexes. Prior animal research frequently used sample sizes that were too small to determine significance with certainty and also did not account for two other factors that influence locomotor performance： age and weight. Our finding is important in light of controversy surrounding the effect of gender on outcome and the fact that SCI affects more than ten thousand new individuals annually, a population that is disproportionately male. By deepening our understanding of why a gender advantage exists, potential new therapeutics can be designed to improve recovery for the male population following the initial trauma or putatively augment the neuroprotective privilege in females for enhanced outcomes.

关键词： sex gender hormone neuroprotection estrogen progesterone apoptosis Schwann cell

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New treatment strategies targeting experimental traumatic brain injury

New treatment strategies targeting experimental traumatic br...

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第七届全国创伤学术会议暨2009海峡两岸创伤医学论坛

作者： w.dalton dietrich Department of Neurological Surgery The Miami Project to Cure Paralysis University of Miami Miller School of Medicine MiamiFL

Traumatic brain injury(TBI) results in significant hippocampal pathology and hippocampal dependent memory loss,both of which have been shown to be improved by hypothermia *** laboratory has been interested in examining the molecular mechanisms regulated by hypothermia after *** example,previous studies have assessed the effects of temperature modifications after brain injury on excitotoxicity, inflammatory and apoptotic cell death *** one recent study,the modulation of the cyclic AMP(cAMP) signaling pathway was evaluated following fluid percussion brain *** observed that TBI leads to prolonged depression of the cAMP/protein kinase A(PKA) pathway in vulnerable brain ***,although phosphodiesterase(PDE) inhibition with the typeⅣinhibitor Rolipram rescued cAMP/PKA signaling cascades,posttraumatic hypothermia had no effect on cyclic AMP levels in this ***,Rolipram treatment reduced overall contusion volume, preserved NeuN positive cells in the overlying cerebral cortex and CA3 hippocampus and inhibited increases in proinflammatory cytokines including IL-1βand TNFα.To determine the molecular pathways involved in the beneficial effects of hypothermia on learning and memory,we also investigated the effects of TBI and temperature modification on protein kinases involved in learning and *** observed that following TBI,various memory kinases including CAMKⅠ,CAMKⅡand CAMKⅣwere transiently elevated in the *** of MAPK and CREB were also ***, posttraumatic hypothermia enhanced MAPK and CREB activation prolonging the elevation of these important signaling *** have recently noticed in our studies evidence for mossy fiber sprouting in the hippocampus after *** brain injury is a major risk factor for the subsequent development of epilepsy,we chose to evaluate the effects of posttraumatic hypothermia on seizure threshold in these *** this end,animals unde

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Gamma-Ray Bursts and Fermi Bubbles

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Journal of High Energy Physics, Gravitation and Cosmology 2023年第2期9卷 496-498页

作者： Kenneth dalton Th. Pongprasart Bang Saphan Prachuap Kiri Khan Thailand

According to a recent calculation, 1058 erg of radiant energy was released by Sgr A*, when it formed the Fermi bubbles. Here, it is argued that this explosion constituted a long gamma-ray burst. .

关键词： Gamma-Ray Burst Supermassive Black Hole

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Eccentric exercise-induced muscle weakness abolishes sex differences in fatigability during sustained submaximal isometric contractions

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运动与健康科学(英文) 2023年第4期12卷 523-533页

作者： Hanna L.Jodoin Avery Hinks Olivia P.Roussel Vincenzo S.Contento Brian H.dalton Geoffrey A.Power Department of Human Health and Nutritional Sciences College of Biological SciencesUniversity of GuelphGuelphON N1G 2W1Canada School of Health and Exercise Science University of British ColumbiaKelownaBC V1V 1V7Canada

Background:Females are typically less fatigable than males during sustained isometric contractions at lower isometric contraction *** sex difference in fatigability becomes more variable during higher intensity isometric and dynamic *** less fatiguing than isometric or concentric contractions,eccentric contractions induce greater and longer lasting impairments in force ***,it is not clear how muscle weakness influences fatigability in males and females during sustained isometric ***:we investigated the effects of eccentric exercise-induced muscle weakness on time to task failure(TTF)during a sustained submaximal isometric contraction in young(18-30 years)healthy males(n=9)and females(n=10).Participants performed a sustained isometric contraction of the dorsiflexors at 35°plantar flexion by matching a 30%maximal voluntary contraction(MVC)torque target until task failure(i.e.,falling below 5%of their target torque for>2 s).The same sustained isometric contraction was repeated 30 min after 150 maximal eccentric *** and antagonist activation were assessed using surface electromyography over the tibialis anterior and soleus muscles,***:Males were~41%stronger than *** eccentric exercise both males and females experienced an~20%decline in maximal voliuntary contraction *** was-34%longer in females than males prior to eccentic exercise-induced muscle ***,following eccentric exercise-induced muscle weakness,this sex-related difference was abolished,with both groups having an"45%shorter ***,there was~100%greater antagonist activation in the female group during the sustained isometric contraction following exercise-induced weakness as compared to the ***:This increase in antagonist activation disadvantaged females by decreasing their TTF,resulting in a blunting of their typical fatigability advantage over males.

关键词： Fatigue Isometric Sex Time to task failure weakness

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It's Proper English, Innit?

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英语世界 2023年第5期 127-128页

作者： A.J.dalton

You can study the English language for years and still not understand a native speaker of English when you meet one. Many language learners know that native speakers say a lot of things that you can’t find in a dictionary. well,here’s a secret for you:a lot of British people can’t understand each other either!

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来源：博看期刊

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道尔顿分压定律

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数理化学习（高中版） 2024年第5期 F0002-F0002页

作者：约翰・道尔顿不详

道尔顿分压定律(也称道尔顿定律)描述的是理想气体的特性。这一经验定律是在1801年由约翰道尔顿所观察得到的。在任何容器内的气体混合物中,如果各组分之间不发生化学反应,则每一种气体都均匀地分布在整个容器内,它所产生的压强和它单... 详细信息

道尔顿分压定律(也称道尔顿定律)描述的是理想气体的特性。这一经验定律是在1801年由约翰道尔顿所观察得到的。在任何容器内的气体混合物中,如果各组分之间不发生化学反应,则每一种气体都均匀地分布在整个容器内,它所产生的压强和它单独占有整个容器时所产生的压强相同。也就是说,一定量的气体在一定容积的容器中的压强仅与温度有关。

关键词：气体混合物经验定律道尔顿定律理想气体道尔顿分压定律化学反应压强容器

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Models and detection of spontaneous recurrent seizures in laboratory rodents

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Zoological Research 2017年第4期38卷 171-179页

作者： Bin Gu Katherine A. dalton Department of Cell Biology and Physiology University of North Carolina Chapel Hill NC 27599 USA Psychology & Neuroscience Program University of North Carofina Chapel Hill NC 27599 USA

Epilepsy, characterized by spontaneous recurrent seizures （SRS）, is a serious and common neurological disorder afflicting an estimated 1% of the population worldwide. Animal experiments, especially those utilizing small laboratory rodents, remain essential to understanding the fundamental mechanisms underlying epilepsy and to prevent, diagnose, and treat this disease. while much attention has been focused on epileptogenesis in animal models of epilepsy, there is little discussion on SRS, the hallmark of epilepsy. This is in part due to the technical difficulties of rigorous SRS detection. In this review, we comprehensively summarize both genetic and acquired models of SRS and discuss the methodology used to monitor and detect SRS in mice and rats.

关键词： Spontaneous recurrent seizures Animal model Epilepsy

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Reviewing guppy color vision： integrating the molecular and physiological variation in visual tuning of a classic system for sensory drive

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Current Zoology 2018年第4期64卷 535-545页

作者： Benjamin SANDKAM Brian dalton Felix BREDEN Karen CARLETON Department of Biology University of Maryland College Park College Park MD 20742 USA Department of Biological Sciences Simon Fraser University Burnaby BC VSA 1S6 Canada

Sensory drive predicts coevolution of mate choice signals with the sensory systems detecting those signals. Guppies are a classic model for sensory drive as mate preferences based on coloration differ across individuals and populations. A large body of work has identified variation in color vision, yet we lack a direct tie between how such variation in color vision influences variation in color preference. Here we bring together studies that have investigated guppy vision over the past 40 years to: (1) highlight our current understanding of where variation occurs in the guppy color vision pathway and (2) suggest future avenues of research into sources of visual system variation that could influence guppy color preference. This will allow researchers to design careful studies that couple measures of color preference with measures of visual system variation from the same individual or population. Such studies will finally provide important answers as to what sets the direction and speed of mate preference evolution via sensory drive.

关键词：颜色视觉开车经典系统分子集成生理配偶选择视觉系统

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