摘要：Spinal cord injury (SCI) interrupts the flow of information between the brain and the spinal cord,thus leading to a loss of sensory information and motor paralysis of the body below the lesion.Surprisingly,most SCIs are incomplete and spare supraspinal pathways,especially those located within the peripheral white matter of the spinal cord,which includes reticulospinal pathways originating from the medullary reticular formation. Whereas there is abundant literature about the motor cortex,its corticospinal pathway,and its capacity to modulate functional recovery after SCI,less is known about the medullary reticular formation and its reticulospinal pathway.

摘要：Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.

摘要：Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders. While the cellular features of aging are complex and multifaceted,neuronal senescence has emerged as a major contributor and driver of this process in the mammalian cell. Cellular senescence is a programmed response to stress and irreparable damage,which drives the cell into an apoptosis-resistant,non-proliferative state. Senescent cells can also deleteriously affect neighboring,non-senescent cells. Senescence is a complex and multifaceted process associated with a wide range of cellular events,including the secretion of pro-inflammatory molecules and the arrest of the cell cycle. Additionally,mitochondrial dysfunction has been broadly demonstrated in senescent cells (Lopez-Otin et al.,2013). Despite their post-mitotic nature,albeit with some controversy,it is now widely accepted that neurons can also display senescence.

摘要：Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain,clear criteria for the stimulation time window and intensity are lacking.Electrical impedance tomography enables real-time monitoring of changes in cerebral blood perfusion within the ischemic brain,but investigating the feasibility of using this method to assess post-stroke rehabilitation in vivo remains critical.In this study,ischemic stroke was induced in rats through middle cerebral artery occlusion surgery.Transcranial focused ultrasound stimulation was used to treat the rat model of ischemia,and electrical impedance tomography was used to measure impedance during both the acute stage of ischemia and the rehabilitation stage following the stimulation.Electrical impedance tomography results indicated that cerebral impedance increased after the onset of ischemia and decreased following transcranial focused ultrasound stimulation.Furthermore,the stimulation promoted motor function recovery,reduced cerebral infarction volume in the rat model of ischemic stroke,and induced the expression of brain-derived neurotrophic factor in the ischemic brain.Our results also revealed a significant correlation between the impedance of the ischemic brain post-intervention and improvements in behavioral scores and infarct volume.This study shows that daily administration of transcranial focused ultrasound stimulation for 20 minutes to the ischemic hemisphere 24 hours after cerebral ischemia enhanced motor recovery in a rat model of ischemia.Additionally,our findings indicate that electrical impedance tomography can serve as a valuable tool for quantitatively evaluating rehabilitation after ischemic stroke in vivo.These findings suggest the feasibility of using impedance data collected via electrical impedance tomography to clinically assess the effects of rehabilitatory interventions for patients with ischemic stroke.

摘要：Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as"fire barriers,"aim to control the spread of neuroinflammation during the acute phase but later hinder axon regeneration in later stages.Recent studies have enhanced our understanding of immunomodulation,revealing that injury-associated inflammation involves various cell types and molecules with positive and negative effects.This review employs bibliometric analysis to examine the literature on inflammatory mediators in spinal cord injury,highlighting recent research and providing a comprehensive overview of the current state of research and the latest advances in studies on neuroinflammation related to spinal cord injury.We summarize the immune and inflammatory responses at different stages of spinal cord injury,offering crucial insights for future research.Additionally,we review repair strategies based on inflammatory mediators for the injured spinal cord.Finally,this review discusses the current status and future directions of translational research focused on immune-targeting strategies,including pharmaceuticals,biomedical engineering,and gene therapy.The development of a combined,precise,and multitemporal strategy for the repair of injured spinal cords represents a promising direction for future research.

摘要：Stroke remains a leading cause of death and disability worldwide,and electroacupuncture has a long history of use in stroke treatment.This meta-analysis and systematic review aimed to evaluate the efficacy of electroacupuncture and explore its potential mechanisms in animal models of ischemic stroke.The PubMed,EMBASE,Web of Science,CENTRAL,and CINAHL databases were comprehensively searched up to May 1,2024.This review included articles on preclinical investigations of the efficacy and mechanisms of electroacupuncture in treating ischemic stroke.Data from 70 eligible studies were analyzed in Stata 18.0,using a random-effects model to calculate the standardized mean difference(Hedge's g).The risk of bias was assessed using RevMan 5.4 software,and the quality of evidence was rated according to the Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)system.Subgroup analyses were conducted to test the consistency of the results and sensitivity analyses were used to assess their robustness.The quality assessment revealed that most studies adequately handled incomplete data and selective reporting.However,several methodological limitations were identified:only 4 studies demonstrated a low risk of allocation concealment,26 achieved a low risk of outcome assessment bias,and 9 had a high risk of randomization bias.Additionally,there was an unclear risk regarding participant blinding and other methodological aspects.The GRADE assessment rated 12 outcomes as moderate quality and 6 as low quality.The mechanisms of electroacupuncture treatment for ischemic stroke can be categorized as five primary pathways:(1)Electroacupuncture significantly reduced infarct volume and apoptotic cell death(P<0.01)in ischemic stroke models;(2)electroacupuncture significantly decreased the levels of pro-inflammatory factors(P<0.01)while increasing the levels of anti-inflammatory factors(P=0.02);(3)electroacupuncture reduced the levels of oxidative stress indicators(P<0.01)and enhanced the expression of antioxidant enzymes(P<0.01);(4)electroacupuncture significantly promoted nerve regeneration(P<0.01);and(5)electroacupuncture influenced blood flow remodeling(P<0.01)and angiogenesis(P<0.01).Subgroup analyses indicated that electroacupuncture was most effective in the transient middle cerebral artery occlusion model(P<0.01)and in post-middle cerebral artery occlusion intervention(P<0.01).Dispersive waves were found to outperform continuous waves with respect to neuroprotection and anti-inflammatory effects(P<0.01),while scalp acupoints demonstrated greater efficacy than body acupoints(P<0.01).The heterogeneity among the included studies was minimal,and sensitivity analyses indicated stable results.Their methodological quality was generally satisfactory.In conclusion,electroacupuncture is effective in treating cerebral ischemia by modulating cell apoptosis,oxidative stress,inflammation,stroke-induced nerve regeneration,blood flow remodeling,and angiogenesis.The efficacy of electroacupuncture may be influenced by factors such as the middle cerebral artery occlusion model,the timing of intervention onset,waveform,and acupoint selection.Despite the moderate to low quality of evidence,these findings suggest that electroacupuncture has clinical potential for improving outcomes in ischemic stroke.

摘要：It was in the 1980s that research on somatostatin(SST) in Alzheimer's disease (AD) truly gained traction,demonstrating consistent colocalization with amyloid-β (Aβ),along with massive SST/SST cell losses(Almeida,2024). Although the field already had some grasp over the neuroendocrine and hypothalamic functions of the peptide,very little was known about the GABAergic interneurons (SST-INs) that synthesize it in cortical/hippocampal regions. Quite excitingly,over 40 years later,research has grown effervescent.Namely,SST-INs show great promise as therapeutic targets for medical intervention in AD and potential players in its aetiopathogenesis. Our perspective aims to provide an update on a molecular model,authored by one of us,which places SST-INs at the fulcrum of AD's aetiopathogenesis (Almeida,2024). In light of spatial constraints,we will lay emphasis specifically on how the SST model is capable of satisfying Occam's razor by placing SST-IN hyperactivity at "stage 0" for neurodegeneration/proteinopathy,and how it sheds light on the paradoxical polarization of p-tau to the hippocampus versus Aβ to the cortex.

摘要：Alzheimer's disease (AD) is the most common form of dementia characterized pathologically by the deposition of amyloid plaques and hyperphosphorylated tau containing neurofibrillary tangles. The disease presents clinically with progressive memory loss and disruption of cognitive function. Currently,there is no cure for AD;recent advances in the therapeutics aimed at clearing the amyloid protein from the brain have led to potential disease stabilization,however,this does not prevent eventual disease progression(Cummings et al.,2024). The mechanisms that cause AD are complex and not fully understood.The main theories for disease development focus on the lack of clearance of amyloid or an increased accumulation of this protein. Changes to brain metabolism,genetic predispositions,inflammation,and the process of aging,all have roles in the establishment of the main sporadic form of the disease.

摘要：Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.

摘要：Tunneling nanotubes are crucial structures for cellular communication and are observed in a variety of cell types.Glial cells,the most abundant cells in the nervous system,play a vital role in intercellular signaling and can show abnormal activation under pathological conditions.Our bibliometric analysis indicated a substantial increase in research on tunneling nanotubes over the past two decades,highlighting their important role in cellular communication.This review focuses on the formation of tunneling nanotubes in various types of glial cells,including astrocytes,microglia,glioma cells,and Schwann cells,as well as their roles in cellular communication and cargo transport.We found that glial cells influence the stability of the neural system and play a role in nerve regeneration through tunneling nanotubes.Tunneling nanotubes facilitate the transmission and progression of diseases by transporting pathogens and harmful substances.However,they are also involved in alleviating cellular stress by removing toxins and delivering essential nutrients.Understanding the interactions between glial cells through tunneling nanotubes could provide valuable insights into the complex neural networks that govern brain function and responses to injury.

摘要：With the gradual advancement of research methods and technologies,various biological processes have been identified as playing roles in the pathogenesis of neurodegenerative diseases.However,current descriptions of these biological processes do not fully explain the onset,progression,and development of these conditions.Therefore,exploration of the pathogenesis of neurodegenerative diseases remains a valuable area of research.This review summarizes the potential common pathogeneses of Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,frontotemporal lobar dementia,and Lewy body disease.Research findings have indicated that several common biological processes,including aging,genetic factors,progressive neuronal dysfunction,neuronal death and apoptosis,protein misfolding and aggregation,neuroinflammation,mitochondrial dysfunction,axonal transport defects,and gut microbiota dysbiosis,are involved in the pathogenesis of these six neurodegenerative diseases.Based on current information derived from diverse areas of research,these biological processes may form complex pathogenic networks that lead to distinctive types of neuronal death in neurodegenerative diseases.Furthermore,promoting the regeneration of damaged neurons may be achievable through the repair of affected neural cells if the underlying pathogenesis can be prevented or reversed.Hence,these potential common biological processes may represent only very small,limited elements within numerous intricate pathogenic networks associated with neurodegenerative diseases.In clinical treatment,interfering with any single biological process has proven insufficient to completely halt the progression of neurodegenerative diseases.Therefore,future research on the pathogenesis of neurodegenerative diseases should focus on uncovering the complex pathogenic networks,rather than isolating individual biological processes.Based on this,therapies that aim to block or reverse various targets involved in the potential pathogenic mechanisms of neurodegenerative diseases may be promising directions,as current treatment methods that focus on halting a single pathogenic factor have not achieved satisfactory efficacy.

摘要：Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter release,and signal transmission,and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases.The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention,but their specific mechanisms remain to be fully understood.This review aims to explore how lipids regulate synaptic activity in the central nervous system,focusing on their roles in synapse formation,neurotransmitter release,and signal transmission.Additionally,it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation.This review shows that within the central nervous system,lipids are essential components of the cell membrane bilayer,playing critical roles in synaptic structure and function.They regulate presynaptic vesicular trafficking,postsynaptic signaling pathways,and glial-neuronal interactions.Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts.Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles.Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis.Fatty acids are vital for energy metabolism and the synthesis of signaling molecules.Abnormalities in lipid metabolism may lead to impairments in synaptic function,affecting information transmission between neurons and the overall health of the nervous system.Therapeutic strategies targeting lipid metabolism,particularly through cholesterol modulation,show promise for treating these conditions.In neurodegenerative diseases such as Alzheimer's disease,Parkinson disease,and amyotrophic lateral sclerosis,dysregulation of lipid metabolism is closely linked to synaptic dysfunction.Therefore,lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs.Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.

摘要：Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography and microelectrode arrays. The challenges of these mentioned approaches are characterized by the bandwidth of the spatiotemporal resolution,which in turn is essential for large-area neuron recordings(Abiri et al.,2019).

摘要：Regenerative capacity of the central nervous system(CNS) is unevenly distributed among vertebrates.While most mammalian species including humans elicit limited repair following CNS injury or disease,highly regenerative vertebrates including urodele amphibians and teleost fish spontaneously reverse CNS damage.Teletost zebrafish (danio rerio) are tropical freshwater fish that proved to be an excellent vertebrate model of successful CNS regeneration. Differential neuronal,glial,and immune injury responses underlie disparate injury outcomes between highly regenerative zebrafish and poorly regenerative mammals. This article describes complications associated with neuronal repair following spinal cord injury (SCI) in poorly regenerative mammals and highlights intersecting modes of plasticity and regeneration in highly regenerative zebrafish (Figures 1 and 2). Comparative approaches evaluating immunoglial SCI responses were recently reviewed elsewhere (Reyes and Mokalled,2024).

摘要：The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.

摘要：The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems. These networks are characterized by two key properties. First,they exhibit dense interconnectivity (Braitenburg and Schüz,1998;Campagnola et al.,2022). The strength and probability of connectivity depend on cell type,inter-neuronal distance,and species.Still,every cortical neuron receives input from thousands of other neurons while transmitting output to a similar number of neurons. Second,communication between neurons occurs primarily via chemical or electrical synapses. The transmission of information is mediated mainly during presynaptic spiking events that generate postsynaptic inward currents and intracellular depolarization,which in turn induce postsynaptic spikes. However,these two properties alone cannot explain the complex mechanisms of information processing in neuronal networks.

摘要：Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the current understanding of the bidirectional relationship between blood-brain barrier disruption and neuroinflammation in traumatic brain injury,along with emerging combination therapeutic strategies.Literature review indicates that blood-brain barrier disruption and neuroinflammatory responses are key pathological features following traumatic brain injury.In the acute phase after traumatic brain injury,the pathological characteristics include primary blood-brain barrier disruption and the activation of inflammatory cascades.In the subacute phase,the pathological features are characterized by repair mechanisms and inflammatory modulation.In the chronic phase,the pathological features show persistent low-grade inflammation and incomplete recovery of the blood-brain barrier.Various physiological changes,such as structural alterations of the blood-brain barrier,inflammatory cascades,and extracellular matrix remodeling,interact with each other and are influenced by genetic,age,sex,and environmental factors.The dynamic balance between blood-brain barrier permeability and neuroinflammation is regulated by hormones,particularly sex hormones and stress-related hormones.Additionally,the role of gastrointestinal hormones is receiving increasing attention.Current treatment strategies for traumatic brain injury include various methods such as conventional drug combinations,multimodality neuromonitoring,hyperbaric oxygen therapy,and non-invasive brain stimulation.Artificial intelligence also shows potential in treatment decision-making and personalized therapy.Emerging sequential combination strategies and precision medicine approaches can help improve treatment outcomes;however,challenges remain,such as inadequate research on the mechanisms of the chronic phase traumatic brain injury and difficulties with technology integration.Future research on traumatic brain injury should focus on personalized treatment strategies,the standardization of techniques,cost-effectiveness evaluations,and addressing the needs of patients with comorbidities.A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.

摘要：The intricate landscape of neurodegenerative diseases complicates the search for effective therapeutic approaches.Photoreceptor degeneration,the common endpoint in various retinal diseases,including retinitis pigmentosa and age-related macular degeneration,leads to vision loss or blindness.While primary cell death is driven by genetic mutations,oxidative stress,and neuroinflammation,additional mechanisms contribute to disease progression.In retinitis pigmentosa,a multitude of genetic alterations can trigger the degeneration of photoreceptors,while other retinopathies,such as age-related macular degeneration,are initiated by combinations of environmental factors,such as diet,smoking,and hypertension,with genetic predispositions.Nutraceutical therapies,which blend the principles of nutrition and pharmaceuticals,aim to harness the health benefits of bioactive compounds for therapeutic applications.These compounds generally possess multi-target effects.Polyphenols and flavonoids,secondary plant metabolites abundant in plant-based foods,are known for their antioxidant,neuroprotective,and anti-inflammatory properties.This review focuses on the potential of polyphenols and flavonoids as nutraceuticals to treat neurodegenerative diseases such as retinitis pigmentosa.Furthermore,the importance of developing reliable delivery methods to enhance the bioavailability and therapeutic efficacy of these compounds will be discussed.By combining nutraceuticals with other emerging therapies,such as genetic and cell-based treatments,it is possible to offer a more comprehensive approach to treating retinal degenerative diseases.These advancements could lead to a viable and accessible option,improving the quality of life for patients with retinal diseases.

摘要：The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions. Gamma-aminobutyric acid (GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time. Notably,recent studies have distinguished two modes of GABA action in the brain:a fast,phasic mode mediated by synaptic GABA release from GABAergic neurons,and a slower,tonic mode resulting from GABA release by non-neuronal cells,particularly astrocytes,which primarily inhibits neuronal activity and synaptic transmission,regulating various cognitive functions (Koh et al.,2023). However,the specific role of tonic GABA effects during the developmental period remains underexplored (Figure 1A). Here,we aim to examine the potential role of astrocytes in regulating GABA tone during development,thereby stimulating further investigation into GABA tone during this critical period.

摘要：The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered "multifactorial" with systemic metabolic alterations. Even so,treatments for neurological disorders have remained unchanged for the past decades. Recently,metabolic drugs such as metformin and glucagon-like peptide 1 agonists have demonstrated promising health outcomes for neurodegeneration.While the exact mechanisms remain to be elucidated,this promotes the repurposing of antidiabetic drugs for cognitive health and redefines neurological disorders as "neurometabolic"disorders. The complexity of systemically acting drugs lies in determining whether their effects are mediated directly through their actions on the brain or indirectly via their peripheral effects.This perspective focuses on the repurposing of metformin for neurological disorders through the remodeling of the myelin landscape.