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1.
Travel Behav Soc ; 30: 1-10, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35965603

ABSTRACT

High-speed railways (HSRs) greatly decrease transportation costs and facilitate the movement of goods, services, and passengers across cities. In the context of the Covid-19 pandemic, however, HSRs may contribute to the cross-regional spread of the new coronavirus. This paper evaluates the role of HSRs in spreading Covid-19 from Wuhan to other Chinese cities. We use train frequencies in 1971 and 1990 as instrumental variables. Empirical results from gravity models demonstrate that one more HSR train originating from Wuhan each day before the Wuhan lockdown increases the cumulative number of Covid-19 cases in a city by about 10 percent. The empirical analysis suggests that other transportation modes, including normal-speed trains and airline flights, also contribute to the spread of Covid-19, but their effects are smaller than the effect of HSRs. This paper's findings indicate that transportation infrastructures, especially HSR trains originating from a city where a pandemic broke out, can be important factors promoting the spread of an infectious disease.

2.
Neural Regen Res ; 18(2): 237-243, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35900397

ABSTRACT

Our ability to learn and remember depends on the active formation, remodeling, and elimination of synapses. Thus, the development and growth of synapses as well as their weakening and elimination are essential for neuronal rewiring. The structural reorganization of synaptic complexes, changes in actin cytoskeleton and organelle dynamics, as well as modulation of gene expression, determine synaptic plasticity. It has been proposed that dysregulation of these key synaptic homeostatic processes underlies the synaptic dysfunction observed in many neurodegenerative diseases. Much is known about downstream signaling of activated N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoazolepropionate receptors; however, other signaling pathways can also contribute to synaptic plasticity and long-lasting changes in learning and memory. The non-receptor tyrosine kinase c-Abl (ABL1) is a key signal transducer of intra and extracellular signals, and it shuttles between the cytoplasm and the nucleus. This review focuses on c-Abl and its synaptic and neuronal functions. Here, we discuss the evidence showing that the activation of c-Abl can be detrimental to neurons, promoting the development of neurodegenerative diseases. Nevertheless, c-Abl activity seems to be in a pivotal balance between healthy synaptic plasticity, regulating dendritic spines remodeling and gene expression after cognitive training, and synaptic dysfunction and loss in neurodegenerative diseases. Thus, c-Abl genetic ablation not only improves learning and memory and modulates the brain genetic program of trained mice, but its absence provides dendritic spines resiliency against damage. Therefore, the present review has been designed to elucidate the common links between c-Abl regulation of structural changes that involve the actin cytoskeleton and organelles dynamics, and the transcriptional program activated during synaptic plasticity. By summarizing the recent discoveries on c-Abl functions, we aim to provide an overview of how its inhibition could be a potentially fruitful treatment to improve degenerative outcomes and delay memory loss.

3.
Neural Regen Res ; 18(2): 253-257, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35900399

ABSTRACT

Although little attention has been paid to cognitive and emotional dysfunctions observed in patients after spinal cord injury, several reports have described impairments in cognitive abilities. Our group also has contributed significantly to the study of cognitive impairments in a rat model of spinal cord injury. These findings are very significant because they demonstrate that cognitive and mood deficits are not induced by lifestyle changes, drugs of abuse, and combined medication. They are related to changes in brain structures involved in cognition and emotion, such as the hippocampus. Chronic spinal cord injury decreases neurogenesis, enhances glial reactivity leading to hippocampal neuroinflammation, and triggers cognitive deficits. These brain distal abnormalities are recently called tertiary damage. Given that there is no treatment for Tertiary Damage, insulin growth factor 1 gene therapy emerges as a good candidate. Insulin growth factor 1 gene therapy recovers neurogenesis and induces the polarization from pro-inflammatory towards anti-inflammatory microglial phenotypes, which represents a potential strategy to treat the neuroinflammation that supports tertiary damage. Insulin growth factor 1 gene therapy can be extended to other central nervous system pathologies such as traumatic brain injury where the neuroinflammatory component is crucial. Insulin growth factor 1 gene therapy could emerge as a new therapeutic strategy for treating traumatic brain injury and spinal cord injury.

4.
Neural Regen Res ; 18(2): 244-252, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35900398

ABSTRACT

Subarachnoid hemorrhage (SAH) is a dominant cause of death and disability worldwide. A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neurons, which subsequently promotes a series of pathophysiological responses leading to neuronal death. Many previous experimental studies have reported that excitotoxicity, mitochondrial death pathways, the release of free radicals, protein misfolding, apoptosis, necrosis, autophagy, and inflammation are involved solely or in combination in this disorder. Among them, irreversible neuronal apoptosis plays a key role in both short- and long-term prognoses after SAH. Neuronal apoptosis occurs through multiple pathways including extrinsic, mitochondrial, endoplasmic reticulum, p53 and oxidative stress. Meanwhile, a large number of blood contents enter the subarachnoid space after SAH, and the secondary metabolites, including oxygenated hemoglobin and heme, further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema, causing early brain injury and delayed cerebral ischemia, and ultimately increasing neuronal apoptosis. Even there is no clear and effective therapeutic strategy for SAH thus far, but by understanding apoptosis, we might excavate new ideas and approaches, as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH. In this review, we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH, which provides a possible target or new strategy for the treatment of SAH.

5.
Neural Regen Res ; 18(2): 267-272, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35900401

ABSTRACT

Multiple sclerosis is a chronic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation, genetic predisposition, and environmental factors. The activation of microglia and astrocytes is a key player in multiple sclerosis immunopathology, playing specific roles associated with anatomical location and phase of the disease and controlling demyelination and neurodegeneration. Even though reactive microglia can damage tissue and heighten deleterious effects and neurodegeneration, activated microglia also perform neuroprotective functions such as debris phagocytosis and growth factor secretion. Astrocytes can be activated into pro-inflammatory phenotype A1 through a mechanism mediated by activated neuroinflammatory microglia, which could also mediate neurodegeneration. This A1 phenotype inhibits oligodendrocyte proliferation and differentiation and is toxic to both oligodendrocytes and neurons. However, astroglial activation into phenotype A2 may also take place in response to neurodegeneration and as a protective mechanism. A variety of animal models mimicking specific multiple sclerosis features and the associated pathophysiological processes have helped establish the cascades of events that lead to the initiation, progression, and resolution of the disease. The colony-stimulating factor-1 receptor is expressed by myeloid lineage cells such as peripheral monocytes and macrophages and central nervous system microglia. Importantly, as microglia development and survival critically rely on colony-stimulating factor-1 receptor signaling, colony-stimulating factor-1 receptor inhibition can almost completely eliminate microglia from the brain. In this context, the present review discusses the impact of microglial depletion through colony-stimulating factor-1 receptor inhibition on demyelination, neurodegeneration, astroglial activation, and behavior in different multiple sclerosis models, highlighting the diversity of microglial effects on the progression of demyelinating diseases and the strengths and weaknesses of microglial modulation in therapy design.

6.
Neural Regen Res ; 18(2): 258-266, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35900400

ABSTRACT

Central nervous system (CNS) trauma, including traumatic brain injury and spinal cord injury, has a high rate of disability and mortality, and effective treatment is currently lacking. Previous studies have revealed that neural inflammation plays a vital role in CNS trauma. As the initial enzyme in neuroinflammation, cytosolic phospholipase A2 (cPLA2) can hydrolyze membranous phosphatides at the sn-2 position in a preferential way to release lysophospholipids and ω3-polyunsaturated fatty acid dominated by arachidonic acid, thereby inducing secondary injuries. Although there is substantial fresh knowledge pertaining to cPLA2, in-depth comprehension of how cPLA2 participates in CNS trauma and the potential methods to ameliorate the clinical results after CNS trauma are still insufficient. The present review summarizes the latest understanding of how cPLA2 participates in CNS trauma, highlighting novel findings pertaining to how cPLA2 activation initiates the potential mechanisms specifically, neuroinflammation, lysosome membrane functions, and autophagy activity, that damage the CNS after trauma. Moreover, we focused on testing a variety of drugs capable of inhibiting cPLA2 or the upstream pathway, and we explored how those agents might be utilized as treatments to improve the results following CNS trauma. This review aimed to effectively understand the mechanism of cPLA2 activation and its role in the pathophysiological processes of CNS trauma and provide clarification and a new referential framework for future research.

7.
Neural Regen Res ; 18(2): 273-279, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35900402

ABSTRACT

Gene deletion has been a valuable tool for unraveling the mysteries of molecular biology. Early approaches included gene trapping and gene targetting to disrupt or delete a gene randomly or at a specific location, respectively. Using these technologies in mouse embryos led to the generation of mouse knockout models and many scientific discoveries. The efficacy and specificity of these approaches have significantly increased with the advent of new technology such as clustered regularly interspaced short palindromic repeats for targetted gene deletion. However, several limitations including unwanted off-target gene deletion have hindered their widespread use in the field. Cre-recombinase technology has provided additional capacity for cell-specific gene deletion. In this review, we provide a summary of currently available literature on the application of this system for targetted deletion of neuronal genes. This article has been constructed to provide some background information for the new trainees on the mechanism and to provide necessary information for the design, and application of the Cre-recombinase system through reviewing the most frequent promoters that are currently available for genetic manipulation of neurons. We additionally will provide a summary of the latest technological developments that can be used for targeting neurons. This may also serve as a general guide for the selection of appropriate models for biomedical research.

8.
Neural Regen Res ; 18(2): 280-283, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35900403

ABSTRACT

Prenatal programming during pregnancy sets physiological outcomes in the offspring by integrating external or internal stimuli. Accordingly, pregnancy is an important stage of physiological adaptations to the environment where the fetus becomes exposed and adapted to the maternal milieu. Maternal exposure to high-energy dense diets can affect motivated behavior in the offspring leading to addiction and impaired sociability. A high-energy dense exposure also increases the pro-inflammatory cytokines profile in plasma and brain and favors microglia activation in the offspring. While still under investigation, prenatal exposure to high-energy dense diets promotes structural abnormalities in selective brain regions regulating motivation and social behavior in the offspring. The current review addresses the role of energy-dense foods programming central and peripheral inflammatory profiles during embryonic development and its effect on motivated behavior in the offspring. We provide preclinical and clinical evidence that supports the contribution of prenatal programming in shaping immune profiles that favor structural and brain circuit disruption leading to aberrant motivated behaviors after birth. We hope this minireview encourages future research on novel insights into the mechanisms underlying maternal programming of motivated behavior by central immune networks.

9.
Neural Regen Res ; 18(2): 284-288, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35900404

ABSTRACT

In the last two years, a new severe acute respiratory syndrome coronavirus (SARS-CoV) infection has spread worldwide leading to the death of millions. Vaccination represents the key factor in the global strategy against this pandemic, but it also poses several problems, especially for vulnerable people such as patients with multiple sclerosis. In this review, we have briefly summarized the main findings of the safety, efficacy, and acceptability of Coronavirus Disease 2019 (COVID-19) vaccination for multiple sclerosis patients. Although the acceptability of COVID-19 vaccines has progressively increased in the last year, a small but significant part of patients with multiple sclerosis still has relevant concerns about vaccination that make them hesitant about receiving the COVID-19 vaccine. Overall, available data suggest that the COVID-19 vaccination is safe and effective in multiple sclerosis patients, even though some pharmacological treatments such as anti-CD20 therapies or sphingosine l-phosphate receptor modulators can reduce the immune response to vaccination. Accordingly, COVID-19 vaccination should be strongly recommended for people with multiple sclerosis and, in patients treated with anti-CD20 therapies and sphingosine l-phosphate receptor modulators, and clinicians should evaluate the appropriate timing for vaccine administration. Further studies are necessary to understand the role of cellular immunity in COVID-19 vaccination and the possible usefulness of booster jabs. On the other hand, it is mandatory to learn more about the reasons why people refuse vaccination. This would help to design a more effective communication campaign aimed at increasing vaccination coverage among vulnerable people.

10.
Neural Regen Res ; 18(2): 289-292, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35900405

ABSTRACT

Traumatic brain injuries are serious clinical incidents associated with some of the poorest outcomes in neurological practice. Coupled with the limited regenerative capacity of the brain, this has significant implications for patients, carers, and healthcare systems, and the requirement for life-long care in some cases. Clinical treatment currently focuses on limiting the initial neural damage with long-term care/support from multidisciplinary teams. Therapies targeting neuroprotection and neural regeneration are not currently available but are the focus of intensive research. Biomaterial-based interventions are gaining popularity for a range of applications including biomolecule and drug delivery, and to function as cellular scaffolds. Experimental investigations into the development of such novel therapeutics for traumatic brain injury will be critically underpinned by the availability of appropriate high throughput, facile, ethically viable, and pathomimetic biological model systems. This represents a significant challenge for researchers given the pathological complexity of traumatic brain injury. Specifically, there is a concerted post-injury response mounted by multiple neural cell types which includes microglial activation and astroglial scarring with the expression of a range of growth inhibitory molecules and cytokines in the lesion environment. Here, we review common models used for the study of traumatic brain injury (ranging from live animal models to in vitro systems), focusing on penetrating traumatic brain injury models. We discuss their relative advantages and drawbacks for the developmental testing of biomaterial-based therapies.

11.
Neural Regen Res ; 18(2): 293-298, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35900406

ABSTRACT

By controlling the proper folding of proteins imported into mitochondria and ensuring crosstalk between the reticulum and mitochondria to modulate intracellular calcium fluxes, Mortalin is a chaperone protein that plays crucial roles in neuronal homeostasis and activity. However, its expression and stability are strongly modified in response to cellular stresses, in particular upon altered oxidative conditions during neurodegeneration. Here, we report and discuss the abundant literature that has highlighted its contribution to the pathophysiology of Parkinson's disease, as well as its therapeutic and prognostic potential in this still incurable pathology.

13.
Neural Regen Res ; 18(2): 299-305, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35900407

ABSTRACT

Currently, there is no cure for traumatic spinal cord injury but one therapeutic approach showing promise is gene therapy. In this systematic review and meta-analysis, we aim to assess the efficacy of gene therapies in pre-clinical models of spinal cord injury and the risk of bias. In this meta-analysis, registered at PROSPERO (Registration ID: CRD42020185008), we identified relevant controlled in vivo studies published in English by searching the PubMed, Web of Science, and Embase databases. No restrictions of the year of publication were applied and the last literature search was conducted on August 3, 2020. We then conducted a random-effects meta-analysis using the restricted maximum likelihood estimator. A total of 71 studies met our inclusion criteria and were included in the systematic review. Our results showed that overall, gene therapies were associated with improvements in locomotor score (standardized mean difference [SMD]: 2.07, 95% confidence interval [CI]: 1.68-2.47, Tau2 = 2.13, I2 = 83.6%) and axonal regrowth (SMD: 2.78, 95% CI: 1.92-3.65, Tau2 = 4.13, I2 = 85.5%). There was significant asymmetry in the funnel plots of both outcome measures indicating the presence of publication bias. We used a modified CAMARADES (Collaborative Approach to Meta-Analysis and Review of Animal Data in Experimental Studies) checklist to assess the risk of bias, finding that the median score was 4 (IQR: 3-5). In particular, reports of allocation concealment and sample size calculations were lacking. In conclusion, gene therapies are showing promise as therapies for spinal cord injury repair, but there is no consensus on which gene or genes should be targeted.

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