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Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise

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Neural Regeneration research 2025年第3期20卷 836-844页

作者： Do-Hun Lee Dan Cao Younghye Moon Chen Chen Nai-Kui Liu Xiao-Ming Xu Wei Wu Spinal Cord and Brain Injury research Group Stark Neurosciences Research InstituteIndiana University School of MedicineIndianapolisINUSA Department of Neurological Surgery Indiana University School of MedicineIndianapolisINUSA Department of neuroscience Baylor College of MedicineHoustonTXUSA

Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

关键词： behavioral assessment motor function neural plasticity running wheel exercise spinal cord injury treadmill exercise voluntary exercise

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DNA methylation program during development

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Frontiers in Biology 2012年第6期7卷 485-494页

作者： Feng C. ZHOU Department of Anatomy and Cell Biology Stark Neuroscience Research Institute Indiana University School Medicine Indianapolis IN46202 USA

DNA methylation is a key epigenetic mark when occurring in the promoter and enhancer regions regulates the accessibility of the binding protein and gene transcription. DNA methylation is inheritable and can be de novosynthesized, erased and reinstated, making it arguably one of the most dynamic upstream regulators for gene expression and the most influential pacer for development. Recent progress has demonstrated that two forms of cytosine methylation and two pathways for demethylation orchestrated gene expression and development. The such a program, if so what the DNA methylation methylation program. The translational implication constitute ample complexity for an instructional program for forum of the current discussion and review are whether there is program entails, and what environment can change the DNA of the DNA methylation program is also proposed.

关键词： epigenetics neural development 5-hydroxymethylcytosine epigenome environmental factors DNA demethylation

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A brief review of recent advances in stem cell biology

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Neural Regeneration research 2014年第7期9卷 684-687页

作者： Jinhui Chen Libing Zhou Su-yue Pan stark neuroscience research institute and Department of Neurological Surgery Indiana University School of Medicine Guangdong-Hongkong-Macao institute of CNS Regeneration (GHMICR) Jinan University Department of Neurology Nanfang Hospital Southern Medical University

Stem cells have the remarkable potential to develop into many different cell types, essentially with- out limit to replenish other cells as long as the person or animal is still alive, offering immense hope of curing Alzheimer＇s disease, repairing damaged spinal cords, treating kidney, liver and lung diseases and making damaged hearts whole. Until recently, scientists primarily worked with two kinds of stem cells from animals and humans： embryonic stem cells and non-embryonic ＂somatic＂ or ＂adult＂ stem cells. Recent breakthrough make it possible to convert or ＂reprogram＂ specialized adult cells to assume a stem stem-like cells with different technologies. The review will briefly dis- cuss the recent progresses in this area.

关键词： stem cell adult stem cell embryonic stem cell somatic cell nuclear transfer induced plu-ripotent stern cell stimulus-triggered acquisition of pluripotency

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Membrane resealing as a promising strategy for early treatment of neurotrauma

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Neural Regeneration research 2014年第21期9卷 1876-1877页

作者： Xiaoming Jin Department of Anatomy and Cell Biology & stark neuroscience research institute Indiana Spinal Cord and Brain Injury Research GroupIndiana University School of Medicine320 West 15th StreetIndianapolisIN 46202USA

Traumatic injuries to the central nervous system （CNS）, in- cluding traumatic brain injury （TBI） and spinal cord injury （SCI）, often involve an immediate mechanical damage to plas- ma membrane that surrounds neuronal sornata and axons. This initial disruption of plasma membrane following injuries has been convincingly demonstrated by increased membrane permeability to large molecules and dyes that are normally inaccessible to cellular plasma （Farkas et al., 2006; Cho and Borgens, 2012）. Further evidence comes from experiments that showed ultra-structural changes of plasma membranes, axons, and organelles, and subsequent neuronal death and axotomy （Povlishock and Pettus, 1996; Whalen et al., 2008）.

关键词： TBI Membrane resealing as a promising strategy for early treatment of neurotrauma

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Potential role of hippocampal neurogenesis in spinal cord injury induced post-trauma depression

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Neural Regeneration research 2024年第10期19卷 2144-2156页

作者： Ying Ma Yue Qiao Xiang Gao Spinal Cord and Brain Injury research Group Stark Neuroscience Research InstituteIndianapolisINUSA Department of Neurological Surgery Indiana University School of MedicineIndianapolisINUSA Department of Neurology Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

It has been reported both in clinic and rodent models that beyond spinal cord injury directly induced symptoms, such as paralysis, neuropathic pain, bladder/bowel dysfunction, and loss of sexual function, there are a variety of secondary complications, including memory loss, cognitive decline, depression, and Alzheimer's disease. The largescale longitudinal population-based studies indicate that post-trauma depression is highly prevalent in spinal cord injury patients. Yet, few basic studies have been conducted to address the potential molecular mechanisms. One of possible factors underlying the depression is the reduction of adult hippocampal neurogenesis which may come from less physical activity, social isolation, chronic pain, and elevated neuroinflammation after spinal cord injury. However, there is no clear consensus yet. In this review, we will first summarize the alteration of hippocampal neurogenesis post-spinal cord injury. Then, we will discuss possible mechanisms underlie this important spinal cord injury consequence. Finally, we will outline the potential therapeutic options aimed at enhancing hippocampal neurogenesis to ameliorate depression.

关键词： antidepressants chronic pain depression exercise hippocampal neurogenesis inflammation inhibition neuroinflammation physical activity deficits social isolation spinal cord injury

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Surgical decompression in acute spinal cord injury： A review of clinical evidence, animal model studies, and potential future directions of investigation

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Frontiers in Biology 2014年第2期9卷 127-136页

作者： Yiping LI Chandler L. WALKER Yi Ping ZHANG Christopher B. SHIELDS Xiao-Ming XU Spinal Cord and Brain Injury research Group Stark Neurosciences Research Institute Department of Neurological Surgery and Goodmanand Campbell Brain and Spine Indiana University School of Medicine Indianapolis IN 46202 USA Norton neuroscience institute Norton Healthcare Louisville KY 40202 USA

The goal for treatment in acute spinal cord injury （SCI） is to reduce the extent of secondary damage and facilitate neurologic regeneration and functional recovery. Although multiple studies have investigated potential new therapies for the treatment of acute SCI, outcomes and management protocols aimed at ameliorating neurologic injury in patients remain ineffective. More recent clinical and basic science research have shown surgical interventions to be a potentially valuable modality for treatment; however, the role and timing of surgical decompression, in addition to the optimal surgical intervention, remain one of the most controversial topics pertaining to surgical treatment of acute SCI. As an increasing number of potential treatment modalities emerge, animal models are pivotal for investigating its clinical application and translation into human trials. This review critically appraises the available literature for both clinical and basic science studies to highlight the extent of investigation that has occurred, specific therapies considered, and potential areas for future research.

关键词： acute spinal cord injury surgical decompression durotomy animal models

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Challenges and opportunities identifying therapeutic targets for chemotherapy-induced peripheral neuropathy resulting from oxidative DNA damage

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Neural Regeneration research 2017年第1期12卷 72-74页

作者： Mark R.Kelley Jill C.Fehrenbacher Pediatric Oncology research Departments of Biochemistry&Molecular Biology and Pharmacology&Toxicology HB Wells Center for Pediatric ResearchBasic Science ResearchIndianaUniversity Simon Cancer CenterIndianapolisINUSA Department of Pharmacology and Toxicology stark neuroscience research institute Department of AnesthesiologyIndiana University School of MedicineIndianapolisINUSA

Background on chemotherapy-induced peripheral neuropathy（CIPN）Incidence,prevalence,and consequences：Up to 90%of cancer patients experience CIPN at some point during or after anticancer treatment（Seretny et al.,201... 详细信息

关键词： neuropathy chemotherapy consequences anticancer identifying oxidative prevalence DNA incidence repair

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Up-regulation of P2X7 Receptors Contributes to Spinal Microglial Activation and the Development of Pain Induced by BmK-I

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neuroscience Bulletin 2019年第4期35卷 624-636页

作者： Jingjing Zhou Xiaoxue Zhang You Zhou Bin Wu Zhi-Yong Tan Laboratory of Neuropharmacology and Neurotoxicology Shanghai University Shanghai 200444 China Department of Pharmacology and Toxicology and stark neurosciences research institute Indiana University School of Medicine Indianapolis IN 46202 USA

Previous work has demonstrated that the sensitization of spinal neurons and microglia is important in the development of pain behaviors induced by BmK I,a Na^+ channel activator and a major peptide component of the venom of the scorpion Buthus martensi Karsch(BmK).We found that the expression of P2X7 receptors(P2X7Rs)was up-regulated in the ipsilateral spinal dorsal horn after BmK I injection in rats.P2X7R was selectively localized in microglia but not astrocytes or ***,interleukin 1β(IL-1β)was selectively up-regulated in microglia in the spinal dorsal horn after BmK I *** injection of P2X7R antagonists largely reduced BmK I-induced spontaneous and evoked pain behaviors,and the up-regulation of P2X7R and IL-1β in the spinal *** data suggested that the up-regulation of P2X7Rs mediates microglial activation in the spinal dorsal horn,and therefore contributes to the development of BmK I-induced pain.

关键词： P2X7 receptor BmK I Spinal dorsal horn Interleukin 1β Microglia Brilliant Blue G

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Current advances in neurotrauma research:diagnosis, neuroprotection,and neurorepair

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Neural Regeneration research 2014年第11期9卷 1093-1095页

作者： Jinhui Chen Riyi Shi Department of Neurological Surgery Stark Neuroscience Research Institute Department of Anatomy Indiana University School of MedicineIndianapolis IN USA Department of Basic Medical Sciences College of Veterinary Medicine Purdue UniversityWest Lafayette IN USA Weldon School of Biomedical Engineering Purdue UniversityWest Lafayette IN USA

Traumatic brain injury （TBI） and spinal cord injury （SCI） causes significant cell death （Raghupathi et al., 1995; DeKosky et al., 1998; Hall et al., 2005; Farkas and Povlishock, 2007） and tissue lesion in the neocortex （Lighthall et al., 1989; Lyeth et al., 1990）, leaving many patients with substantial motor dis- ability and cognitive impairment （Harem et al., 1992; Scheff et al., 1997）. Unfortunately, at present, there are no clinically demonstrated FDA approved drug therapies for treatment of TBI and SCI patients that reduce the neurological injuries. Thus, TBI and SCI are serious health problems. The devel- opment of therapeutic approaches to prevent neuronal death and enhance neuroregeneration for promoting post-traumat- ic functional recovery would be of enormous clinical, social, and economic benefits. The reviews in this specific issue focus largely on the current progress on diagnosis, neuroprotection, and potential neurorepair with stem cells.

关键词： TBI NSCs neuroprotection,and neurorepair

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Immunological Markers for Central Nervous System Glia

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neuroscience Bulletin 2023年第3期39卷 379-392页

作者： Hao Huang Wanjun He Tao Tang Mengsheng Qiu Zhejiang Key Laboratory of Organ Development and Regeneration Institute of Life SciencesCollege of Life and Environmental SciencesHangzhou Normal UniversityHangzhou 311121China Department of Anatomy Cell Biology and Physiology Stark Neurosciences Research InstituteIndiana University School of MedicineIndianapolisIN 46202USA

Glial cells in the central nervous system(CNS)are composed of oligodendrocytes,astrocytes and *** contribute more than half of the total cells of the CNS,and are essential for neural development and *** on the fate specification,differentiation,and functional diversification of glial cells mainly rely on the proper use of cell-or stage-specific molecular ***,as cellular markers often exhibit different specificity and sensitivity,careful consideration must be given prior to their application to avoid possible ***,we provide an updated overview of a list of well-established immunological markers for the labeling of central glia,and discuss the cell-type specificity and stage dependency of their expression.

关键词： Glial cells Oligodendrocytes Astrocytes Microglia Markers

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