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Blood-brain barrier pathology in cerebral small vessel disease

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 Anatomy Radboud University Medical Center Donders Institute for Brain Cognition & Behavior Center for Medical Neuroscience Preclinical Imaging Center PRIME Radboud Alzheimer Center

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly. Although at first it was considered innocuous, small vessel disease is nowadays regarded as one of the major vascular causes of dementia. Radiological 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 patients. The pathophysiology of these lesions has been linked to multiple processes, such as hypoperfusion, defective cerebrovascular reactivity, and blood-brain barrier dysfunction. Notably, 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 disease. Therefore, the purpose of this review is to provide a new foundation in the study of small vessel disease pathology. First, we discuss the main structural domains and functions of the blood-brain barrier. Secondly, we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease. Finally, 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

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Intermittent Theta Burst Stimulation Attenuates Cognitive Deficits and Alzheimer’s Disease-Type Pathologies via ISCA1-Mediated Mitochondrial Modulation in APP/PS1 Mice

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neuroscience Bulletin 2024年第2期40卷 182-200页

作者： Yang Zhu Hao Huang Zhi Chen Yong Tao Ling-Yi Liao Shi-Hao Gao Yan-Jiang Wang Chang-Yue Gao department of Rehabilitation Medicine Daping HospitalArmy Medical UniversityChongqing 400042China department of Neurology and Center for Clinical neuroscience Daping HospitalArmy Medical UniversityChongqing 400042China department of Special Medicine Daping HospitalArmy Medical UniversityChongqing 400042China

Intermittent theta burst stimulation(iTBS),a time-saving and cost-effective repetitive transcranial magnetic stimulation regime,has been shown to improve cognition in patients with Alzheimer’s disease(AD).However,the specific mechanism underlying iTBS-induced cognitive enhancement remains *** studies suggested that mitochondrial functions are modulated by magnetic ***,we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1(ISCA1,an essential regulatory factor for mitochondrial respiration)in the brain of APP/PS1 *** vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function,which is required for ***,iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 *** present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in *** provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.

关键词： Intermittent theta burst stimulation Alzheimer’s disease Iron-sulfur cluster assembly 1 Mitochondrial dysfunction Neurodegeneration

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Exploring cerebral structural and functional abnormalities in a mouse model of post-traumatic headache induced by mild traumatic brain injury

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Zoological Research 2024年第3期45卷 648-662页

作者： Dan Yang Bin-Bin Nie Jin-Gang He Zong-Qiang Lv Feng-Feng Mo Si-Yi Ouyang Jie Wang Ju-Xiang Chen Tao Tao department of anesthesiology Central People’s Hospital of ZhanjiangZhanjiangGuangdong 524045China Key Laboratory of Nuclear Radiation and Nuclear Energy Technology Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsNational Center for Magnetic Resonance in WuhanWuhan Institute of Physics and MathematicsInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of Sciences-Wuhan National Laboratory for OptoelectronicsWuhanHubei 430071China department of Neurosurgery Changhai HospitalNaval Medical UniversityShanghai 200082China department of Nutrition and Food Hygiene Faculty of Naval MedicineNaval Medical UniversityShanghai 200433China department of anesthesiology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Institute of neuroscience and Brain Diseases/Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and ScienceXiangyangHubei 441021China Songjiang Hospital and Songjiang Research Institute Shanghai Jiao Tong University School of MedicineShanghai 201600China department of anesthesiology Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China

Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability *** PTH is often accompanied by neurological disorders,the exact underlying mechanism remains largely *** potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced *** this study,a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term *** indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury *** kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum,temporal lobe/cortex,and hippocampal regions during the early stages of ***,variations in brain functional activities and connectivity were further detected in the early stage of PTH,particularly in the cerebellum and temporal cortex,suggesting that these regions play central roles in the mechanism underlying ***,our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for *** studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex,with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.

关键词： Post-traumatic headache(PTH) Mild traumatic brain injury(mTBI) Metabolic kinetics fMRI Cerebellum

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Tau's function and dysfunction in the brain:when small changes have big consequences

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Neural Regeneration Research 2024年第1期19卷 152-153页

作者： Miguel Portillo Debra Toiber department of Life Sciences Ben-Gurion University of the NegevBeer ShevaIsraelThe Zlotowski Center for NeuroscienceBen-Gurion University of the NegevBeer ShevaIsrael

With the increase of life expectancy and population growth,neurodegenerative diseases have risen too and are projected to be a major health public concern by *** diseases are characterized by the progressive decline of cognitive function leading to the subsequent loss of *** the underlying causes of neurodegeneration are not well understood,aging is the main risk factor.

关键词： diseases consequences function

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Modifying the progression of Parkinson's disease through movement interventions:multimodal quantification of underlying mechanisms

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Neural Regeneration Research 2024年第8期19卷 1651-1652页

作者： Manuel Bange Damian Marc Herz Dumitru Ciolac Gabriel Gonzalez-Escamilla Sergiu Groppa Section of Movement Disorders and Neurostimulation Department of NeurologyFocus Program Translational Neuroscience(FTN)University Medical Center of the Johannes Gutenberg-University MainzMainzGermany

Introduction:Parkinson’s disease(PD)is the most common neurodegenerative movement *** pathological hallmark is the progressive loss of dopaminergic neurons of the substantia nigra pars compacta,which is accompanied by widespread alterations in the structu re and function of distributed brain *** r,these processes cause a variety of motor symptoms such as bradykinesia,rigidity,tremor,gait disorders,or difficulties in fine motor control(Bange et al.,2022).

关键词： alterations movement

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Genetic pathways in cerebral palsy:a review of the implications for precision diagnosis and understanding disease mechanisms

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Neural Regeneration Research 2024年第7期19卷 1499-1508页

作者： Yiran Xu Yifei Li Seidu A.Richard Yanyan Sun Changlian Zhu Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center Institute of Neuroscience and The Third Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina National Health Council(NHC)Key Laboratory of Birth Defects Prevention Henan Key Laboratory of Population Defects PreventionZhengzhouHenan ProvinceChina department of Human Anatomy School of Basic Medicine and Institute of NeuroscienceZhengzhou UniversityZhengzhouHenan ProvinceChina Center for Brain Repair and Rehabilitation Institute of Neuroscience and PhysiologyUniversity of GothenburgGothenburgSweden

Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and *** with cerebral palsy are often only capable of limited activity,resulting from non-progressive disturbances in the fetal or neonatal *** disturbances severely impact the child’s daily life and impose a substantial economic burden on the *** cerebral palsy encompasses various brain injuries leading to similar clinical outcomes,the unde rstanding of its etiological pathways remains incomplete owing to its complexity and *** review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy *** is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development,which can be further influenced by environmental fa *** pite continuous research endeavors,the underlying fa ctors contributing to cerebral palsy remain are still ***,significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy *** r,these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping,including thrombosis,angiogenesis,mitochondrial and oxidative phosphorylation function,neuronal migration,and cellular ***,exploring targeted genotypes holds potential for precision *** conclusion,advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral *** breakthroughs have the potential to pave the way for new treatments and therapies,consequently shaping the future of cerebral palsy research and its clinical *** investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management *** elucidating the underlying cellular mechanisms,w

关键词： cerebral palsy environmental factors etiology genetic factors genetic mutation movement disorder spastic diplegia

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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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Neurogenesis dynamics in the olfactory bulb:deciphering circuitry organization, function, and adaptive plasticity

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Neural Regeneration Research 2025年第6期20卷 1565-1581页

作者： Moawiah M.Naffaa department of Psychology and neuroscience Duke UniversityDurhamNCUSA department of Cell Biology Duke University School of MedicineDurhamNCUSA

Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased

关键词： network adaptability neurogenesis neuronal communication olfactory bulb olfactory learning olfactory memory synaptic plasticity

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enOsCas12f1-mediated exon skipping for Duchenne muscular dystrophy therapy in humanized mouse model

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Journal of Genetics and Genomics 2024年第2期51卷 256-259页

作者： Ming Jin Jiajia Lin Yu Zhang Qingquan Xiao Xiangfeng Kong Xiumei Zhang Zhurui Shao Yin Wang Yuyang Yu Jinjing Li Wan-Jin Chen Guoling Li Hui Yang Ning Wang department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of NeuroscienceFujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian 350004China HUIDAGENE Therapeutics Co. Ltd.Shanghai 200131China Institute of neuroscience State Key Laboratory of NeuroscienceKey Laboratory of Primate NeurobiologyCAS Center for Excellence in Brain Science and Intelligence TechnologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China

Duchenne muscular dystrophy(DMD)is a severe neuromuscular disorder caused by mutations in the dystrophin gene,which encodes the essential protein *** genetic condition,affecting approximately 1 in 5000 male births worldwide(Birnkrant et al.,2018),is characterized by progressive muscle weakness and wasting,leading to premature death in the second or third decade of life(Farini et al.,2016).The absence of dystrophin protein causes instability in the sarcolemma,which predisposes individuals to myonecrosis and activation of inflammatory signaling ***,there is currently no effective cure for DMD,and glucocorticoid steroids are commonly used in clinical settings to delay symptom development(Merlini et al.,2003).

关键词： dystrophy Duchenne

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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

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