Experimental Neurology最新文献

{"title":"Activation of PAR1 contributes to ferroptosis of Schwann cells and inhibits regeneration of myelin sheath after sciatic nerve crush injury in rats via Hippo-YAP/ACSL4 pathway","authors":"Zhimin Wu ,&nbsp;Jun Sun ,&nbsp;Zhi Liao ,&nbsp;Tao Sun ,&nbsp;Lixin Huang ,&nbsp;Jia Qiao ,&nbsp;Cong Ling ,&nbsp;Chuan Chen ,&nbsp;Baoyu Zhang ,&nbsp;Hui Wang","doi":"10.1016/j.expneurol.2024.115053","DOIUrl":"10.1016/j.expneurol.2024.115053","url":null,"abstract":"<div><h3>Objective</h3><div>Peripheral nerve injury (PNI) is characterized by high incidence and sequela rate. Recently, there was increasing evidence that has shown ferroptosis may impede functional recovery. Our objective is to explore the novel mechanism that regulates ferroptosis after PNI.</div></div><div><h3>Methods</h3><div>LC-MS/MS proteomics was used to explore the possible differential signals, while PCR array was performed to investigate the differential factors. Besides, we also tried to activate or inhibit the key factors and then observe the level of ferroptosis. Regeneration of myelin sheath was finally examined in vivo via transmission electron microscopy.</div></div><div><h3>Results</h3><div>Proteomics analysis suggested coagulation signal was activated after sciatic nerve crush injury, in which high expression of <em>F2</em> (encoding thrombin) and <em>F2r</em> (encoding PAR1) were observed. Both thrombin and PAR1-targeted activator TRAP6 can induce ferroptosis in RSC96 cells, which can be rescued by Vorapaxar (PAR1 targeted inhibitor) in vitro. Further PCR array revealed that activation of PAR1 induced ferroptosis in RSC96 cells by increasing expression of YAP and ACSL4. Immunofluorescence of sciatic nerve confirmed that the expression of YAP and ACSL4 were simultaneously reduced after PAR1 inhibition, which may contribute to myelin regeneration after injury in SD rats.</div></div><div><h3>Conclusion</h3><div>Inhibition of PAR1 can relieve ferroptosis after sciatic nerve crush injury in SD rats through Hippo-YAP/ACSL4 pathway, thereby regulating myelin regeneration after injury. In summary, PAR1/Hippo-YAP/ACSL4 pathway may be a promising therapeutic target for promoting functional recovery post-sciatic crush injury.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115053"},"PeriodicalIF":4.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conceptualization and standardization of a non-invasive closed head injury model using directed shockwave to mice","authors":"Mohd Aleem,&nbsp;Princy Verma,&nbsp;Kailash Manda","doi":"10.1016/j.expneurol.2024.115051","DOIUrl":"10.1016/j.expneurol.2024.115051","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with closed head injury (CHI) being one of the most common forms of TBI. Preclinical modeling of TBI is challenging due to confounding factors like craniectomy and poorly controlled injury severity. This study proposes a non-invasive CHI model using directed shockwaves. The mice heads were exposed to the shockwave and accommodated together following the implantation of RFID tags for automated neurocognitive assessment. Following a 13-days paradigm, mice underwent a digital gait analysis and subsequent classical behavioral test paradigms for affective, cognitive, and locomotor functions. Qualitative and quantitative histopathological assessment was carried out for shockwave pulses-dependent changes in terms of lesion volume, neuronal death, dendritic complexity, and spine density. Studies showed shockwave pulses-dependent differences in survivability, righting reflex, neural damage, and death. Shockwave-exposed mice showed significantly impaired learning and cognitive flexibility. Interestingly, exposed mice showed locomotor hyperactivity and risk-taking behavior (lack of anxiety) along with depression-like phenotypes. Our result suggests that the shockwave-based CHI models result in the clinically relevant phenotype and are precisely controlled for reproducibility.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115051"},"PeriodicalIF":4.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling of TDP-43 proteinopathy by chronic oxidative stress identifies rapamycin as beneficial in ALS patient-derived 2D and 3D iPSC models","authors":"Valeria Casiraghi ,&nbsp;Marta Nice Sorce ,&nbsp;Serena Santangelo ,&nbsp;Sabrina Invernizzi ,&nbsp;Patrizia Bossolasco ,&nbsp;Chiara Lattuada ,&nbsp;Cristina Battaglia ,&nbsp;Marco Venturin ,&nbsp;Vincenzo Silani ,&nbsp;Claudia Colombrita ,&nbsp;Antonia Ratti","doi":"10.1016/j.expneurol.2024.115057","DOIUrl":"10.1016/j.expneurol.2024.115057","url":null,"abstract":"<div><div>Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterized neuropathologically by TDP-43 proteinopathy with loss of TDP-43 nuclear splicing activity and formation of cytoplasmic TDP-43 aggregates. The lack of suitable experimental models of TDP-43 proteinopathy has hampered the discovery of effective therapies. We already showed that chronic and mild oxidative insult by sodium arsenite (ARS) triggered TDP-43 cytoplasmic aggregation and stress granules (SGs) formation in ALS patient-derived fibroblasts and motor neurons differentiated from induced pluripotent stem cells (iPSC-MNs). However, whether this insult induces a reduction of TDP-43 splicing activity in the nucleus, thus recapitulating both gain and loss of function pathomechanisms, still remains to be determined.</div><div>In this study we first showed that chronic ARS in human neuroblastoma cells triggered TDP-43 cytoplasmic mislocalization, SGs formation and defective splicing of TDP-43 target genes <em>UNC13A</em> and <em>POLDIP3</em> as functional readouts of TDP-43 proteinopathy. Additionally, a dysregulation of autophagy and senescence markers was observed in this condition. In a preliminary drug screening approach with autophagy-promoting drugs, namely rapamycin, lithium carbonate and metformin, only rapamycin prevented ARS-induced loss of TDP-43 splicing activity. We then demonstrated that, in addition to TDP-43 cytoplasmic aggregation, chronic ARS triggered TDP-43 loss of splicing activity also in ALS patient-derived primary fibroblasts and iPSC-MNs and that rapamycin was beneficial to reduce these TDP-43 pathological features. By switching to a neuro-glial 3D <em>in vitro</em> model, we observed that treatment of ALS iPSC-brain organoids with chronic ARS also induced a defective TDP-43 splicing activity which was prevented by rapamycin.</div><div>Collectively, we established different human cell models of TDP-43 proteinopathy which recapitulate TDP-43 gain and loss of function, prevented by rapamycin administration. Human neuroblastoma cells and patient-derived fibroblasts and 2D- and 3D-iPSC models exposed to chronic oxidative stress represent therefore suitable <em>in vitro</em> platforms for future drug screening approaches in ALS.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"383 ","pages":"Article 115057"},"PeriodicalIF":4.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sevoflurane aggravates cognitive impairment in OSAS mice through tau phosphorylation and mitochondrial dysfunction","authors":"Feixiang Li ,&nbsp;Dujuan Li ,&nbsp;Bingqing Gong ,&nbsp;Zichen Song ,&nbsp;Yang Yu ,&nbsp;Yonghao Yu ,&nbsp;Yongyan Yang","doi":"10.1016/j.expneurol.2024.115056","DOIUrl":"10.1016/j.expneurol.2024.115056","url":null,"abstract":"<div><div>With an aging population, the incidence of obstructive sleep apnea syndrome (OSAS) is rising, resulting in a growing number of patients undergoing surgery who are also affected by OSAS. The combined impact of anesthetic drugs and OSAS-related neurological damage has drawn significant attention. Here, wild-type (WT) and Tau-knockout (Tau-KO) mice were subjected to intermittent hypoxia and sevoflurane exposure to induce OSAS and sevoflurane-induced neurotoxicity. Protein expression of tau phosphorylation (Tau-Ser202/Thr205 and Tau-Ser422) was measured by Western blotting. Immunofluorescence was used to visualize tau phosphorylation (Tau-Ser202/Thr205) in the hippocampal CA1 region. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP levels. Cognitive functions were assessed using the Morris water maze and Y-maze tests. We found that compared to the WT OSAS group, sevoflurane significantly increased tau phosphorylation and mitochondrial dysfunction in WT OSAS mice, leading to cognitive impairment. Interestingly, idebenone treatment mitigated sevoflurane-induced mitochondrial dysfunction and cognitive impairment in WT OSAS mice, but it did not affect tau phosphorylation. Compared to the Tau-KO control group, Tau-KO OSAS mice exhibited mitochondrial dysfunction and cognitive impairment, but sevoflurane did not exacerbate mitochondrial dysfunction or cognitive impairment in these mice. These findings suggest that sevoflurane exacerbates cognitive impairments in OSAS mice through tau phosphorylation-induced mitochondrial dysfunction, but also uncovered differing mechanisms between cognitive impairments induced by OSAS and those exacerbated by sevoflurane.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115056"},"PeriodicalIF":4.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking new Frontiers: The cellular and molecular impact of extracorporeal shock wave therapy (ESWT) on central nervous system (CNS) disorders and peripheral nerve injuries (PNI)","authors":"Baodan Cao ,&nbsp;Xiaobin Tang ,&nbsp;Chuangjian Liu ,&nbsp;Guangyu Xu ,&nbsp;Mingcheng Lei ,&nbsp;Fan Wu ,&nbsp;Wei Chen ,&nbsp;Hongbin Ni ,&nbsp;Feng Zhang","doi":"10.1016/j.expneurol.2024.115052","DOIUrl":"10.1016/j.expneurol.2024.115052","url":null,"abstract":"<div><div>Neurological disorders encompassing both central nervous system (CNS) diseases and peripheral nerve injuries (PNI), represent significant challenges in modern clinical practice. Conditions such as stroke, spinal cord injuries, and carpal tunnel syndrome can cause debilitating impairments, leading to reduced quality of life and placing a heavy burden on healthcare systems. Current treatment strategies, including pharmacological interventions and surgical procedures, often yield limited results, and many patients experience suboptimal outcomes or treatment-associated risks. In light of these limitations, there is a growing interest in exploring non-invasive therapeutic alternatives. Among these, extracorporeal shock wave therapy (ESWT) has eme rged as a promising modality, demonstrating efficacy in musculoskeletal conditions and gaining attention for its potential role in neurological disorders. This manuscript aims to provide a comprehensive overview of the cellular and molecular mechanisms underlying ESWT, focusing on its therapeutic applications in CNS diseases and PNI, thereby shedding light on its potential to revolutionize the treatment landscape for neurological conditions.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115052"},"PeriodicalIF":4.6,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of GABAergic system as a therapeutic option in stroke","authors":"Milka Perovic ,&nbsp;Damjan Pavlovic ,&nbsp;Zoe Palmer ,&nbsp;Mariana S.B. Udo ,&nbsp;Cristiane T. Citadin ,&nbsp;Krista M. Rodgers ,&nbsp;Celeste Yin-Chien Wu ,&nbsp;Quanguang Zhang ,&nbsp;Hung Wen Lin ,&nbsp;Vesna Tesic","doi":"10.1016/j.expneurol.2024.115050","DOIUrl":"10.1016/j.expneurol.2024.115050","url":null,"abstract":"<div><div>Stroke is one of the leading causes of death and permanent adult disability worldwide. Despite the improvements in reducing the rate and mortality, the societal burden and costs of treatment associated with stroke management are increasing. Most of the therapeutic approaches directly targeting ischemic injury have failed to reduce short- and long-term morbidity and mortality and more effective therapeutic strategies are still needed to promote post-stroke functional recovery. Decades of stroke research have been focused on hyperexcitability and glutamate-induced excitotoxicity in the acute phase of ischemia and their relation to motor deficits. Recent advances in understanding the pathophysiology of stroke have been made with several lines of evidence suggesting that changes in the neurotransmission of the major inhibitory system via γ-Aminobutyric acid (GABA) play a particularly important role in functional recovery and deserve further attention. The present review provides an overview of how GABAergic neurotransmission changes correlate with stroke recovery and outlines GABAergic system modulators with special emphasis on neurosteroids that have been shown to affect stroke pathogenesis or plasticity or to protect against cognitive decline. Supporting evidence from both animal and human clinical studies is presented and the potential for GABA signaling-targeted therapies for stroke is discussed to translate this concept to human neural repair therapies. Age and sex are considered crucial parameters related to the pathophysiology of stroke and important factors in the development of therapeutic pharmacological strategies. Future work is needed to deepen our knowledge of the neurochemical changes after stroke, extend the conceptual framework, and allow for the development of more effective interventions that include the modulation of the inhibitory system.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115050"},"PeriodicalIF":4.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing data standards to advance translation in spinal cord injury","authors":"Vanessa K. Noonan ,&nbsp;Suzanne Humphreys ,&nbsp;Fin Biering-Sørensen ,&nbsp;Susan Charlifue ,&nbsp;Yuying Chen ,&nbsp;James D. Guest ,&nbsp;Linda A.T. Jones ,&nbsp;Jennifer French ,&nbsp;Eva Widerström-Noga ,&nbsp;Vance P. Lemmon ,&nbsp;Allen W. Heinemann ,&nbsp;Jan M. Schwab ,&nbsp;Aaron A. Phillips ,&nbsp;Marzieh Mussavi Rizi ,&nbsp;John L.K. Kramer ,&nbsp;Catherine R. Jutzeler ,&nbsp;Abel Torres-Espin","doi":"10.1016/j.expneurol.2024.115048","DOIUrl":"10.1016/j.expneurol.2024.115048","url":null,"abstract":"<div><div>Data standards are available for spinal cord injury (SCI). The International SCI Data Sets were created in 2002 and there are currently 27 freely available. In 2014 the National Institute of Neurological Disorders and Stroke developed clinical common data elements to promote clinical data sharing in SCI. The objective of this paper is to provide an overview of SCI data standards, describe learnings from the traumatic brain injury (TBI) field using data to enhance research and care, and discuss future opportunities in SCI. Given the complexity of SCI, frameworks such as a systems medicine approach and Big Data perspective have been advanced. Implementation of these frameworks require multi-modal data and a shift towards open science and principles such as requiring data to be FAIR (Findable, Accessible, Interoperable and Reusable). Advanced analytics such as artificial intelligence require data to be interoperable so data can be exchanged among different technology systems and software applications. The TBI field has multiple ongoing initiatives to promote sharing and data reuse for both pre-clinical and clinical studies, which is an opportunity for the SCI field given these injuries can often occur concomitantly. The adoption of interoperable standards, data sharing, open science, and the use of advanced analytics in SCI is needed to facilitate translation in research and care. It is critical that people with lived experience are engaged to ensure data are relevant and enhances quality of life.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115048"},"PeriodicalIF":4.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein tau phosphorylation in the proline rich region and its implication in the progression of Alzheimer's disease","authors":"Paula Merino-Serrais ,&nbsp;José Miguel Soria ,&nbsp;Cristina Aguirre Arrabal ,&nbsp;Alfonso Ortigado-López ,&nbsp;María Ángeles García Esparza ,&nbsp;Alberto Muñoz ,&nbsp;Félix Hernández ,&nbsp;Jesús Ávila ,&nbsp;Javier DeFelipe ,&nbsp;Gonzalo León-Espinosa","doi":"10.1016/j.expneurol.2024.115049","DOIUrl":"10.1016/j.expneurol.2024.115049","url":null,"abstract":"<div><div>Tau has a wide variety of essential functions in the brain, but this protein also plays a determining role in the development of Alzheimer's disease (AD) and other neurodegenerative diseases called tauopathies. This is due to its abnormal aggregation and the subsequent formation of neurofibrillary tangles. Tau hyperphosphorylation appears to be a critical step in its transformation into an aggregated protein. However, the exact process, including the cellular events that trigger it, remains unclear. In this study, we employed immunocytochemistry assays on hippocampal sections from AD cases and from tauopathy cases (Braak stage III) with no evidence of cognitive decline, and the P301S mouse model to investigate the colocalization patterns of Tau phosphorylated (p) at specific residues (S202-T205, S214, and T231) within the proline-rich region. Our results show pyramidal neurons in the hippocampus of P301S mice in which Tau is intensely phosphorylated at residues S202 and T205 (recognized by the AT8 antibody), but with no detectable phosphorylation at S214 or T231. These non-colocalizing neurons displayed intensely labeled aggregated pTau deposits distributed through the soma and dendritic processes. However, most of the hippocampal pyramidal neurons are labeled with pTauS214 or pTauT231 antibodies and typically showed a homogeneous and diffuse pTau distribution (not aggregated). This different labeling likely reflects a Tau conformational step, potentially related to the transition from a diffuse tau phosphorylation phenotype (Type 2) into an NFT-like or Type 1 phenotype. We further observed that dendrites of CA3 pyramidal cells are intensely labeled with pTau214 in the <em>stratum lucidum</em>, but not with AT8 or pTauT231. By contrast, analysis of tissue from AD patients or other human tauopathy cases (Braak stage III) with no evidence of cognitive decline revealed extensive colocalization with both antibody combinations in CA1. The complete or mature tangle development may follow a different mechanism in the P301S mouse model or may require more time to achieve the maturity state found in AD cases. Further studies would be necessary to address this question.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"383 ","pages":"Article 115049"},"PeriodicalIF":4.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAPK signaling pathway in spinal cord injury: Mechanisms and therapeutic potential","authors":"Fei-xiang Lin ,&nbsp;Hou-yun Gu ,&nbsp;Wei He","doi":"10.1016/j.expneurol.2024.115043","DOIUrl":"10.1016/j.expneurol.2024.115043","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a severe disabling injury of the central nervous system that can lead to motor, sensory, and autonomic dysfunction below the level of the injury. According to its pathophysiological process, SCI can be divided into primary injury and secondary injury. Currently, multiple therapeutic strategies have been proposed to alleviate secondary injury and overcome the occurrence of neurodegenerative events. Although current treatment modalities have achieved varying degrees of success, they cannot effectively intervene or treat its pathological processes, which may be due to the complex treatment and protection mechanisms involved. Research has confirmed that signaling pathways play a crucial role in the pathological processes of SCI and the mechanisms of neuronal recovery. Mitogen-activated protein kinase (MAPK) signaling pathway plays a crucial role in neuronal differentiation, growth, survival and axon regeneration after central nervous system injury. Meanwhile, the MAPK signaling pathway is an important pathway closely related to the pathological processes of SCI. The MAPK signaling pathway is abnormally activated after SCI, and inhibiting the activity of MAPK pathway can effectively inhibit inflammation, oxidative stress, pain and apoptosis to promote the recovery of nerve function after SCI. Based on the role of the MAPK pathway in SCI, it may be a potential therapeutic target. This article summarizes the role and mechanism of MAPK pathway in SCI, and discusses the shortcomings and shortcomings of MAPK pathway in SCI field, as well as the potential challenges of targeting MAPK pathway in SCI treatment strategies. This article aims to elucidate the mechanism of the MAPK pathway in SCI to emphasize the role of targeting the MAPK pathway in the treatment of SCI, providing a theoretical basis for the MAPK pathway as a potential therapeutic target for SCI treatment.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"383 ","pages":"Article 115043"},"PeriodicalIF":4.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of time-restricted feeding-induced neuroprotection and neuronal plasticity in ischemic stroke as a function of circadian rhythm","authors":"Soomin Jeong ,&nbsp;Charles K. Davis ,&nbsp;Raghu Vemuganti","doi":"10.1016/j.expneurol.2024.115045","DOIUrl":"10.1016/j.expneurol.2024.115045","url":null,"abstract":"<div><div>Time-restricted feeding (TRF) is known to promote longevity and brain function, and potentially prevent neurological diseases. Animal studies show that TRF enhances brain-derived neurotrophic factor (BDNF) signaling and regulates autophagy and neuroinflammation, supporting synaptic plasticity, neurogenesis and neuroprotection. Feeding/fasting paradigms influence the circadian cycle, with TRF aligning circadian cycle-related gene expression, and thus altering physiological processes. Emerging evidence highlights the role of gut microbiota in neuronal plasticity, based on the observation that TRF significantly alters gut microbiota composition. Hence, the gut-brain axis may be crucial for maintaining cognitive functions and presents a potential therapeutic target for TRF-mediated neuroprotection. In the context of ischemic stroke where neuronal damage is extensive, TRF can be a preconditioning strategy to enhance synaptic plasticity and neuronal resilience, thus improving outcomes after stroke. This review discussed the link between TRF and circadian regulation in neuronal plasticity and its implications for recovery after stroke.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"383 ","pages":"Article 115045"},"PeriodicalIF":4.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}