Experimental Neurology最新文献

{"title":"Microglial mitochondrial DNA release contributes to neuroinflammation after intracerebral hemorrhage through activating AIM2 inflammasome","authors":"Feng Gu ,&nbsp;Zongqi Wang ,&nbsp;Haojie Ding ,&nbsp;Xinyu Tao ,&nbsp;Juyi Zhang ,&nbsp;Kun Dai ,&nbsp;Xiang Li ,&nbsp;Haitao Shen ,&nbsp;Haiying Li ,&nbsp;Zhouqing Chen ,&nbsp;Zhong Wang","doi":"10.1016/j.expneurol.2024.114950","DOIUrl":"10.1016/j.expneurol.2024.114950","url":null,"abstract":"<div><p>Intracerebral hemorrhage (ICH) is a severe disease that often leads to disability and death. Neuroinflammatory response is a key causative factor of early secondary brain injury after ICH. AIM2 is a DNA-sensing protein that recognizes cytosolic double-stranded DNA and take a significant part in neuroinflammation. Mitochondrial DNA participates in the translation of proteins such as the respiratory chain in the mitochondria. Whether mtDNA is involved in forming AIM2 inflammasome after ICH remains unclear. We used mice to construct ICH model in vivo and we used BV2 microglial cells treated with oxyhemoglobin to simulate ICH in vitro. Following lentiviral transfection to overexpress AIM2 antagonist P202, a notable decrease was observed in the levels of AIM2 inflammasome-associated proteins, leading to a reduction in dead neurons surrounding the hematoma and an enhancement in long-term and short-term behavior of neurological deficits. We further explored whether mtDNA took part in the AIM2 activation after ICH. The cytosolic mtDNA level was down-regulated by the mitochondrial division protector Mdivi-1 and up-regulated by transfection of mtDNA into cytoplasm. We found the expression level of AIM2 inflammasome-related proteins and inflammatory cytokines release were regulated by the cytosolic mtDNA level. In conclusion, after ICH, the mtDNA content in the cytoplasm of microglia around the hematoma rises, causing AIM2 inflammation leading to neuronal apoptosis, which leads to neurological deficits in mice. On the other hand, P202 was able to block inflammatory vesicle activation and improve neurological function by preventing the interaction between AIM2 protein and mitochondrial DNA.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239086","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":"CHCHD10P80L knock-in zebrafish display a mild ALS-like phenotype","authors":"Virginie Petel Légaré ,&nbsp;Ziyaan A. Harji ,&nbsp;Christian J. Rampal ,&nbsp;Hana Antonicka ,&nbsp;Tyler J.N. Gurberg ,&nbsp;Olivia Persia ,&nbsp;Esteban C. Rodríguez ,&nbsp;E.A. Shoubridge ,&nbsp;Gary A.B. Armstrong","doi":"10.1016/j.expneurol.2024.114945","DOIUrl":"10.1016/j.expneurol.2024.114945","url":null,"abstract":"<div><p>Mutations in the nuclear-encoded mitochondrial gene <em>CHCHD10</em> have been observed in patients with a spectrum of diseases that include amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). To investigate the pathogenic nature of disease-associated variants of CHCHD10 we generated a zebrafish knock-in (KI) model expressing the orthologous ALS-associated CHCHD10^P80L variant (zebrafish: Chchd10^P83L). Larval <em>chchd10</em>^P83L/P83L fish displayed reduced Chchd10 protein expression levels, motor impairment, reduced survival and abnormal neuromuscular junctions (NMJ). These deficits were not accompanied by changes in transcripts involved in the integrated stress response (ISR), phenocopying previous findings in our knockout (<em>chchd10</em>^−/−). Adult, 11-month old <em>chchd10</em>^P83L/P83L zebrafish, displayed smaller slow- and fast-twitch muscle cell cross-sectional areas compared to wild type zebrafish muscle cells. Motoneurons in the spinal cord of <em>chchd10</em>^P83L/P83L zebrafish displayed similar cross-sectional areas to that of wild type motor neurons and significantly fewer motor neurons were observed when compared to <em>chchd2</em>^−/− adult spinal cords. Bulk RNA sequencing using whole spinal cords of 7-month old fish revealed transcriptional changes associated with neuroinflammation, apoptosis, amino acid metabolism and mt-DNA inflammatory response in our <em>chchd10</em>^P83L/P83L model. The findings presented here, suggest that the <em>CHCHD10</em>^P80L variant confers an ALS-like phenotype when expressed in zebrafish.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014488624002711/pdfft?md5=acebd485cd331dc0d00349d10242a947&pid=1-s2.0-S0014488624002711-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219019","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":"Connecting the dots: Involvement of methyltransferase-like 3, N6-methyladenosine modification, and ferroptosis in the pathogenesis of intracerebral hemorrhage pathogenesis","authors":"Junxiang Mao ,&nbsp;Quantang Zhao ,&nbsp;Man Guo ,&nbsp;Shenghao Zhang ,&nbsp;Jie Zhou","doi":"10.1016/j.expneurol.2024.114948","DOIUrl":"10.1016/j.expneurol.2024.114948","url":null,"abstract":"<div><p>Intracerebral hemorrhage is a profoundly detrimental acute cerebrovascular condition with a low overall survival rate and a high post-onset disability rate. Secondary brain injury that ensues post-ICH is the primary contributor to fatality and disability. Hence, the mitigation of brain injury during intracerebral hemorrhage progression has emerged as a crucial aspect of clinical management. N6-methyladenosine is the most pervasive, abundant, and conserved internal co-transcriptional modification of eukaryotic ribonucleic acid and is predominantly expressed in the nervous system. Methyltransferase-like 3 is a key regulatory protein that is strongly associated with the development of the nervous system and numerous neurological diseases. Ferroptosis, a form of iron-associated cell death, is a typical manifestation of neuronal apoptosis in neurological diseases and plays an important role in secondary brain damage following intracerebral hemorrhage. Therefore, this review aimed to elucidate the connection between m6A modification (particularly methyltransferase-like 3) and ferroptosis in the context of intracerebral hemorrhage to provide new insights for future intracerebral hemorrhage management approaches.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219001","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":"Human cranial bone-derived mesenchymal stem cells cultured under simulated microgravity can improve cerebral infarction in rats","authors":"Masashi Kuwabara ,&nbsp;Takafumi Mitsuhara ,&nbsp;Masataka Teranishi ,&nbsp;Takahito Okazaki ,&nbsp;Masaaki Takeda ,&nbsp;Daizo Ishii ,&nbsp;Hiroshi Kondo ,&nbsp;Kiyoharu Shimizu ,&nbsp;Masahiro Hosogai ,&nbsp;Takeshi Hara ,&nbsp;Yuyo Maeda ,&nbsp;Tomoyuki Kurose ,&nbsp;Yumi Kawahara ,&nbsp;Louis Yuge ,&nbsp;Nobutaka Horie","doi":"10.1016/j.expneurol.2024.114947","DOIUrl":"10.1016/j.expneurol.2024.114947","url":null,"abstract":"<div><p>The efficacy of transplanting human cranial bone-derived mesenchymal stem cells (hcMSCs) cultured under simulated microgravity (sMG) conditions has been previously reported; however, their effect on cerebral infarction remains unknown. Here, we examined the efficacy of transplanting hcMSCs cultured in an sMG environment into rat models of cerebral infarction. For evaluating neurological function, hcMSCs cultured in either a normal gravity (1G) or an sMG environment were transplanted in rats 1 day after inducing cerebral infarction. The expression of endogenous neurotrophic, axonal, neuronal, synaptogenic, angiogenic, and apoptosis-related factors in infarcted rat brain tissue was examined using real-time polymerase chain reaction and western blotting 35 days after stroke induction. The RNAs of hcMSCs cultured under 1G or sMG environments were sequenced. The results showed that neurological function was significantly improved after transplantation of hcMSCs from the sMG group compared with that from the 1G group. mRNA expressions of nerve growth factor, fibroblast growth factor 2, and synaptophysin were significantly higher in the sMG group than in the 1G group, whereas sortilin 1 expression was significantly lower. RNA sequencing analysis revealed that genes related to cell proliferation, angiogenesis, neurotrophy, neural and synaptic organization, and inhibition of cell differentiation were significantly upregulated in the sMG group. In contrast, genes promoting microtubule and extracellular matrix formation and cell adhesion, signaling, and differentiation were downregulated. These results demonstrate that hcMSCs cultured in the sMG environment may be a useful source of stem cells for the recovery of neurological function after cerebral infarction.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232172","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":"A deep learning-based approach for unbiased kinematic analysis in CNS injury","authors":"Maureen C. Ascona ,&nbsp;Ethan Kim Tieu ,&nbsp;Erick Gonzalez-Vega ,&nbsp;Daniel J. Liebl ,&nbsp;Roberta Brambilla","doi":"10.1016/j.expneurol.2024.114944","DOIUrl":"10.1016/j.expneurol.2024.114944","url":null,"abstract":"<div><p>Traumatic spinal cord injury (SCI) is a devastating condition that impacts over 300,000 individuals in the US alone. Depending on the severity of the injury, SCI can lead to varying degrees of sensorimotor deficits and paralysis. Despite advances in our understanding of the underlying pathological mechanisms of SCI and the identification of promising molecular targets for repair and functional restoration, few therapies have made it into clinical use. To improve the success rate of clinical translation, more robust, sensitive, and reproducible means of functional assessment are required. The gold standards for the evaluation of locomotion in rodents with SCI are the Basso Beattie Bresnahan (BBB) scale and Basso Mouse Scale (BMS).</p><p>To overcome the shortcomings of current methods, we developed two separate markerless kinematic analysis paradigms in mice, MotorBox and MotoRater, based on deep-learning algorithms generated with the DeepLabCut open-source toolbox. The MotorBox system uses an originally designed, custom-made chamber, and the MotoRater system was implemented on a commercially available MotoRater device. We validated the MotorBox and MotoRater systems by comparing them with the traditional BMS test and extracted metrics of movement and gait that can provide an accurate and sensitive representation of mouse locomotor function post-injury, while eliminating investigator bias and variability. The integration of MotorBox and/or MotoRater assessments with BMS scoring will provide a much wider range of information on specific aspects of locomotion, ensuring the accuracy, rigor, and reproducibility of behavioral outcomes after SCI.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S001448862400270X/pdfft?md5=e0c149582e1dc6ef94ee392d883ce4c0&pid=1-s2.0-S001448862400270X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145490","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":"Ferroptosis in the neurovascular unit after spinal cord injury","authors":"Yushan Huang ,&nbsp;Jinzhu Bai","doi":"10.1016/j.expneurol.2024.114943","DOIUrl":"10.1016/j.expneurol.2024.114943","url":null,"abstract":"<div><p>The mechanisms of secondary injury following spinal cord injury are complicated. The role of ferroptosis, which is a newly discovered form of regulated cell death in the neurovascular unit(NVU), is increasingly important. Ferroptosis inhibitors have been shown to improve neurovascular homeostasis and attenuate secondary spinal cord injury(SCI). This review focuses on the mechanisms of ferroptosis in NVU cells and NVU-targeted therapeutic strategies according to the stages of SCI, and analyzes possible future research directions.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014488624002693/pdfft?md5=9ed018ed2cb983f145963e58e55be83f&pid=1-s2.0-S0014488624002693-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145491","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":"In vitro modelling of the neurovascular unit for ischemic stroke research: Emphasis on human cell applications and 3D model design","authors":"Bo Pang,&nbsp;Lei Wu,&nbsp;Ying Peng","doi":"10.1016/j.expneurol.2024.114942","DOIUrl":"10.1016/j.expneurol.2024.114942","url":null,"abstract":"<div><p>Ischemic stroke has garnered global medical attention as one of the most serious cerebrovascular diseases. The mechanisms involved in both the development and recovery phases of ischemic stroke are complex, involving intricate interactions among different types of cells, each with its own unique functions. To better understand the possible pathogenesis, neurovascular unit (NVU), a concept comprising neurons, endothelial cells, mural cells, glial cells, and extracellular matrix components, has been used in analysing various brain diseases, particularly in ischemic stroke, aiming to depict the interactions between cerebral vasculature and neural cells. While in vivo models often face limitations in terms of reproducibility and the ability to precisely mimic human pathophysiology, it is now important to establish in vitro NVU models for ischemic stroke research. In order to accurately portray the pathological processes occurring within the brain, a diverse array of NVU 2D and 3D in vitro models, each possessing unique characteristics and advantages, have been meticulously developed. This review presents a comprehensive overview of recent advancements in in vitro models specifically tailored for investigating ischemic stroke. Through a systematic categorization of these developments, we elucidate the intricate links between NVU components and the pathogenesis of ischemic stroke. Furthermore, we explore the distinct advantages offered by innovative NVU models, notably 3D models, which closely emulate in vivo conditions. Additionally, an examination of current therapeutic modalities for ischemic stroke developed utilizing in vitro NVU models is provided. Serving as a valuable reference, this review aids in the design and implementation of effective in vitro models for ischemic stroke research.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119277","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":"Physical exercise as a cognitive rehabilitation treatment after traumatic brain injury: Intensity- and sex-dependent effects","authors":"Ángel Gómez-Porcuna,&nbsp;Meritxell Torras-Garcia ,&nbsp;Margalida Coll-Andreu,&nbsp;Soleil García-Brito,&nbsp;David Costa-Miserachs","doi":"10.1016/j.expneurol.2024.114941","DOIUrl":"10.1016/j.expneurol.2024.114941","url":null,"abstract":"<div><p>We investigated the effects of forced physical exercise (PE) intensity on cognitive dysfunction and histological changes associated with traumatic brain injury (TBI), in both male and female rats. Controlled cortical impact (CCI) produced similar short- and long-term memory deficits in both sexes, and these deficits were associated with reduced volume and neuronal loss in the hippocampus, but not with changes in neurogenesis. We found sex differences in the effects of intensity of forced PE on cognitive recovery: all PE intensities tested improved short-term memory in both sexes, but to a greater extent in females, while long-term memory benefits were intensity- and sex-dependent. Males benefited most from low-intensity PE, while females showed optimal results at moderate intensity. These optimal PE intensities increased the neurogenesis in both sexes. A neuroprotective effect of low-intensity PE was evident in males, but no effect was observed in females. These findings suggest an intensity- and sex-specific effect of PE post-TBI, emphasizing the need for tailored PE protocols based on sex to enhance therapeutic outcomes.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S001448862400267X/pdfft?md5=224d9e36dc71e024d711eaabb135644a&pid=1-s2.0-S001448862400267X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105924","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":"Simvastatin exerts neuroprotective effects post-stroke by ameliorating endoplasmic reticulum stress and regulating autophagy/apoptosis balance through pAMPK/LC3B/ LAMP2 axis","authors":"Bijoyani Ghosh ,&nbsp;Aishika Datta ,&nbsp;Vishal Gupta ,&nbsp;Babasaheb Sodnar ,&nbsp;Abhishek Sarkar ,&nbsp;Upasna Singh ,&nbsp;Swapnil Raut ,&nbsp;Pramod Suthar ,&nbsp;Vrushali Thongire ,&nbsp;Deepaneeta Sarmah ,&nbsp;Harpreet Kaur ,&nbsp;Anupom Borah ,&nbsp;Shailendra Saraf ,&nbsp;Pallab Bhattacharya","doi":"10.1016/j.expneurol.2024.114940","DOIUrl":"10.1016/j.expneurol.2024.114940","url":null,"abstract":"<div><p>Statins have evident neuroprotective role in acute ischemic stroke(AIS). The pleiotropic effect by which statin exerts neuroprotective effects, needs to be explored for considering it as one of the future adjunctive therapies in AIS. Endoplasmic reticulum(ER) assists cellular survival by reducing protein aggregates during ischemic conditions. ER-stress mediated apoptosis and autophagy are predominant reasons for neuronal death in AIS. Statin exerts both anti-apoptotic and anti-autophagic effect in neurons under ischemic stress. Although the influence of statin on autophagic neuroprotection has been reported with contradictory results. Thus, in our study we have attempted to understand its influence on autophagic protection while inhibiting upregulation of autophagic death(autosis). Previously we reported, statin can alleviate apoptosis via modulating cardiolipin mediated mitochondrial dysfunction. However, the clearance of damaged mitochondria is essential for prolonged cell survival. In our study, we tried to decipher the mechanism by which statin leads to neuronal survival by the mitophagy mediated cellular clearance. Simvastatin was administered to Sprague Dawley(SD) rats both as prophylaxis and treatment. The safety and efficacy of the statin was validated by assessment of infarct size and functional outcome. A reduction in oxidative and ER-stress were observed in both the prophylactic and treatment groups. The influence of statin on autophagy/apoptosis balance was evaluated by molecular assessment of mitophagy and cellular apoptosis. Statin reduces the post-stroke ER-stress and predominantly upregulated autophagolysosome mediated mitophagy than apoptotic cell death by modulating pAMPK/LC3B/LAMP2 axis. Based on the above findings statin could be explored as an adjunctive therapy for AIS in future.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105925","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":"Recurrent endothelin-1 mediated vascular insult leads to cognitive impairment protected by trophic factor pleiotrophin","authors":"Mayank Pushpam ,&nbsp;Ankita Talukdar ,&nbsp;Shobha Anilkumar ,&nbsp;Shashank Kumar Maurya ,&nbsp;Thomas Gregor Issac ,&nbsp;Latha Diwakar","doi":"10.1016/j.expneurol.2024.114938","DOIUrl":"10.1016/j.expneurol.2024.114938","url":null,"abstract":"<div><p>Vascular dementia (VaD) is a complex neurodegenerative condition, with cerebral small vessel dysfunctions as the central role in its pathogenesis. Given the lack of suitable animal models to study the disease pathogenesis, we developed a mouse model to closely emulate the clinical scenarios of recurrent transient ischemic attacks (TIAs) leading to VaD using vasoconstricting peptide Endothelin-1(ET-1). We observed that administration of ET-1 led to blood-brain barrier (BBB) disruption and detrimental changes in its components, such as endothelial cells and pericytes, along with neuronal loss and synaptic dysfunction, resulting in irreversible memory loss. Further, in our pursuit of understanding potential interventions, we co-administered pleiotrophin (PTN) alongside ET-1 injections. PTN exhibited remarkable efficacy in preserving vital components of the BBB, including endothelial cells and pericytes, thereby restoring BBB integrity, preventing neuronal loss, and enhancing memory function. Our findings give a valuable framework for understanding the detrimental effects of multiple TIAs on brain health and provide a useful animal model to explore VaD's underlying mechanisms further and pave the way for promising therapies.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092572","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}