Neurochemistry international最新文献

{"title":"Honokiol-induced SIRT3 upregulation protects hippocampal neurons by suppressing inflammatory processes in pilocarpine-induced status epilepticus","authors":"Soojin Park ,&nbsp;Soomi Cho ,&nbsp;Kyung Min Kim ,&nbsp;Min Kyung Chu ,&nbsp;Chul Hoon Kim ,&nbsp;Kyoung Hoon Jeong ,&nbsp;Won-Joo Kim","doi":"10.1016/j.neuint.2024.105873","DOIUrl":"10.1016/j.neuint.2024.105873","url":null,"abstract":"<div><div>Status epilepticus (SE), a continuous and self-sustaining epileptic seizure lasting more than 30 min, is a neurological emergency that can cause severe brain injuries and increase the risk for the development of epilepsy. Over the past few decades, accumulating evidence has suggested the importance of brain inflammation in the pathogenesis of epilepsy. Honokiol (HNK), a pharmacological activator of sirtuin 3 (SIRT3), is a bioactive compound extracted from the bark or leaves of Magnolia plants that possesses therapeutic benefits for preventing the development of inflammatory injury. However, the therapeutic effects of HNK against epileptic brain injury via regulating molecular mechanisms related to neuroinflammation remains elusive. Therefore, the present study investigated the effects of HNK on pilocarpine-induced status epilepticus (PCSE) and the therapeutic benefits of HNK in regulating inflammatory processes in the hippocampus. Treatment with HNK before PCSE induction attenuated the initiation of behavioral seizures. Post-treatment with HNK after SE onset increased SIRT3 expression, which mitigated glial activation, including reactive astrocytes and activated microglia, in the hippocampus following PCSE. Moreover, HNK treatment reduced the activation of the nuclear factor-κB/nucleotide-binding domain leucine-rich repeat with a pyrin-domain containing 3 inflammasome pathway, thereby inhibiting the production of interleukin-1β pro-inflammatory cytokine, subsequently alleviating PCSE-triggered apoptotic neuronal death in the hippocampus. These results indicate that HNK-induced SIRT3 upregulation has the potential to prevent the progression of epileptic neuropathology through its anti-inflammatory properties. Therefore, the present study suggests that HNK is a natural therapeutic agent for epileptic brain injury.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105873"},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacopa monnieri confers neuroprotection by influencing signaling pathways associated with interleukin 4, 13 and extracellular matrix organization in Alzheimer's disease: A proteomics-based perspective","authors":"Akhina Palollathil ,&nbsp;Mohd Altaf Najar ,&nbsp;S. Amrutha ,&nbsp;Ravishankar Pervaje ,&nbsp;Prashant Kumar Modi ,&nbsp;Thottethodi Subrahmanya Keshava Prasad","doi":"10.1016/j.neuint.2024.105864","DOIUrl":"10.1016/j.neuint.2024.105864","url":null,"abstract":"<div><div>Alzheimer's disease, a prevalent neurodegenerative disorder in the elderly, is characterized by the accumulation of senile plaques and neurofibrillary tangles, triggering oxidative stress, neuroinflammation, and neuronal apoptosis. Current therapies focus on symptomatic treatment rather than targeting the underlying disease-modifying molecular mechanisms and are often associated with significant side effects. <em>Bacopa monnieri</em>, a traditional Indian herb with nootropic properties, has shown promise in neurological disorder treatment from ancient times. However, its mechanisms of action in Alzheimer's disease remain elusive. In this study, a cellular model for Alzheimer's disease was created by treating differentiated IMR-32 cells with beta-amyloid, 1–42 peptide (Aβ₄₂). Additionally, a recovery model was established through co-treatment with <em>Bacopa monnieri</em> to explore its protective mechanism. Co-treatment with <em>Bacopa monnieri</em> extract recovered Aβ₄₂ induced damage as evidenced by the decreased apoptosis and reduced reactive oxygen species production. Mass spectrometry-based quantitative proteomic analysis identified 21,674 peptides, corresponding to 3626 proteins from the Alzheimer's disease model. The proteins dysregulated by Aβ₄₂ were implicated in cellular functions, such as negative regulation of cell proliferation and microtubule cytoskeleton organization. The enriched pathways include extracellular matrix organization and interleukin-4 and interleukin-13 signaling. <em>Bacopa monnieri</em> co-treatment showed remarkable restoration of Aβ₄₂ altered proteins, including <em>FOSL1,</em> and <em>TDO2</em>. The protein-protein interaction network analysis of <em>Bacopa monnieri</em> restored proteins identified the hub gene involved in Alzheimer's disease. The findings from this study may open up new avenues for creating innovative therapeutic approaches for Alzheimer's disease.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105864"},"PeriodicalIF":4.4,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the role of cholecystokinin in epilepsy: Mechanistic insight into neuroplasticity","authors":"Muhammad Asim ,&nbsp;Gao Qianqian ,&nbsp;Abdul Waris ,&nbsp;Huajie Wang ,&nbsp;Yuanying Lai ,&nbsp;Xi Chen","doi":"10.1016/j.neuint.2024.105870","DOIUrl":"10.1016/j.neuint.2024.105870","url":null,"abstract":"<div><div>Epilepsy is a disorder characterized by an imbalance between excitability and inhibition, leading to uncontrolled hyperexcitability of neurons in the central nervous system. Despite the prevalence of epileptic seizures, the underlying mechanisms driving this hyperexcitability remain poorly understood. This review article aims to enhance our understanding of the mechanisms of epilepsy, with a specific focus on the role of cholecystokinin (CCK) in this debilitating disease. We will begin with an introduction to the topic, followed by an examination of the role of GABAergic neurons and the synaptic plasticity mechanisms associated with seizures. As we delve deeper, we will elucidate how CCK and its receptors contribute to seizure behavior. Finally, we will discuss the CCK-dependent synaptic plasticity mechanisms and highlight their potential implications in seizure activity. Through a comprehensive examination of these aspects, this review provides valuable insights into the involvement of CCK and its receptors in epilepsy. By improving our understanding of the mechanisms underlying this condition, particularly the role of CCK, we aim to contribute to the development of more effective treatment strategies.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105870"},"PeriodicalIF":4.4,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effects of Withania somnifera on ischemic stroke are mediated via anti-inflammatory response and modulation of neurotransmitter levels","authors":"Abhilasha Sood ,&nbsp;Arpit Mehrotra ,&nbsp;Devinder K. Dhawan ,&nbsp;Rajat Sandhir","doi":"10.1016/j.neuint.2024.105867","DOIUrl":"10.1016/j.neuint.2024.105867","url":null,"abstract":"<div><div>The present study was designed to evaluate the beneficial effects of hydroalcoholic root extract of <em>Withania somnifera</em> (WS) on ischemia-reperfusion injury (IRI) induced by Middle Cerebral Artery Occlusion (MCAO). MCAO animals showed increase in IL-6, TNF-α and MCP-1 levels in terms of mRNA and protein levels. Concomitantly, mRNA and protein levels for astrocyte and microglial activation markers; GFAP and IBA-1, were increased in MCAO animals. COX-2 and NF-kβ protein levels were also increased in the brains of MCAO animals. The levels of neurotransmitters; glutamate and GABA were increased in the MCAO animals. On the contrary, levels of catecholamines; dopamine, norepinephrine and serotonin were reduced in the MCAO animals. Additionally, MCAO animals showed reduced locomotor activity. However, pre-supplementation with WS hydro-alcoholic root extract at a dose of 300 mg/kg, body weight to MCAO animals reduced the expression of IL-6, TNF-α and MCP-1. In addition, WS also reduced the number of GFAP and Iba-1 positive cells in comparison to MCAO animals. WS pre-supplementation was also observed to inhibit MCAO induced increase in COX-2; NF-kβ proteins and reduce the glutamate levels. The levels of GABA, dopamine, norepinephrine and serotonin were increased in WS pre-supplemented MCAO animals. WS pre-supplementation also prevented motor deficits in the MCAO animals. Taken together, these findings suggest that WS is effective in attenuating IRI induced neuroinflammation, neurochemical alterations and motor deficits in MCAO model of ischemic stroke thereby suggesting its ameliorative role in ischemia-reperfusion injury.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105867"},"PeriodicalIF":4.4,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phyto-nanotechnology: A novel beneficial strategy for Alzheimer's disease therapy","authors":"Shayeri Chatterjee Ganguly ,&nbsp;Sk Sangram ,&nbsp;Sayani Paul ,&nbsp;Moumita Kundu","doi":"10.1016/j.neuint.2024.105868","DOIUrl":"10.1016/j.neuint.2024.105868","url":null,"abstract":"<div><div>Alzheimer's disease, a neurodegenerative condition, is characterized by the slow and progressive deterioration of the cognitive functions of geriatric patients. It occurs due to exacerbation of neurons in the brain, indicated by loss of memory, mood instability, and even death. The aggregation of amyloid β protein and neurofibrillary tangles-atypical forms of tau protein is the major cause of this disease. Phytoconstituents have been frequently employed in treating Alzheimer's disease. These natural compounds act through different molecular mechanisms to treat the disease. However, their potential in Alzheimer's disease therapy may be limited due to poor blood-brain barrier permeability, off-target effects, low bioavailability, etc. In recent times, nanotechnology has gained attraction to overcome these challenges. This article focuses on the potential phytoconstituents for Alzheimer's disease treatment and the associated limitations. Moreover, it highlights various nanoformulation strategies employed to penetrate the blood-brain barrier effectively, avoid side effects, improve bioavailability, and target specificity in treating Alzheimer's disease. The integration of nanotechnology with plant-derived compounds has the potential to revolutionize the therapeutic landscape for Alzheimer's disease.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105868"},"PeriodicalIF":4.4,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effect of vitamin B12 supplementation on cognitive functions and neuronal morphology at different time intervals after traumatic brain injury in male Swiss albino mice","authors":"Priyanka Yadav,&nbsp;Farheen Nasir,&nbsp;Thamil Mani Sivanandam","doi":"10.1016/j.neuint.2024.105869","DOIUrl":"10.1016/j.neuint.2024.105869","url":null,"abstract":"<div><div>Traumatic brain injury is a highly irreversible process that consists of primary as well as secondary injury which develops and progresses over months to years, leading to cognitive dysfunctions. Vitamin B₁₂ received considerable interest due to its potential therapeutic properties. The pathways of vitamin B₁₂ are closely related to neuronal survival but its effects on the pathophysiology of injury with respect to cognition is a relatively unexplored area of research. In this study, we investigated, the effect of vitamin B₁₂ and its involvement in neuroprotection on TBI-induced pathophysiology in male Swiss albino mice. Our findings suggested that vitamin B₁₂ supplementation improves TBI-mediated neurological impairments, spatial and recognition memory, and anxiety-like behavior. Furthermore, the oxidative stress was reduced by declined homocysteine level with vitamin B₁₂ supplementation validating declined expression of astrocytes and TBI biomarkers. The studies on neuronal morphology revealed that vitamin B₁₂ supplementation increases the dendritic arborization and density of mushroom and filopodia-shaped spines and further increases the expression of synaptic plasticity-related genes and proteins. Taken together, our findings reveal that, supplementation of vitamin B₁₂ restored the TBI-induced downregulation of dendritic arborization, and spine density which ultimately increases synaptic plasticity, cell survival, and recovery of cognitive dysfunctions.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105869"},"PeriodicalIF":4.4,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statins ameliorate oxaliplatin- and paclitaxel-induced peripheral neuropathy via glutathione S-transferase","authors":"Fuka Aizawa ,&nbsp;Haruna Kajimoto ,&nbsp;Ami Okabayashi ,&nbsp;Daishi Moriyama ,&nbsp;Kenta Yagi ,&nbsp;Shimon Takahashi ,&nbsp;Yuhei Sonoda ,&nbsp;Takahiro Shibata ,&nbsp;Mitsuhiro Goda ,&nbsp;Takahiro Niimura ,&nbsp;Yuki Izawa-Ishizawa ,&nbsp;Hirofumi Hamano ,&nbsp;Kei Kawada ,&nbsp;Yoshito Zamami ,&nbsp;Keisuke Ishizawa","doi":"10.1016/j.neuint.2024.105863","DOIUrl":"10.1016/j.neuint.2024.105863","url":null,"abstract":"<div><div>Some therapeutic agents have been found to have effects beyond their primary indications. Peripheral neuropathy, a common side effect of chemotherapy, remains inadequately treated. Identifying additional properties of existing medications could thus uncover novel therapeutic avenues. Previous studies have identified an additional effect of simvastatin in reducing neuropathy; however, the mechanism underlying this effect remains unclear. We investigated the novel effects of statins on chemotherapy-induced peripheral neuropathy in mice. Mice treated with oxaliplatin or paclitaxel did not show exacerbation or improvement in cold sensations upon acetone testing with statin administration. However, concurrent oral statin treatment mitigated the nociceptive response to mechanical stimuli induced by each anti-tumor agent. Co-administration of a glutathione S-transferase inhibitor, which modulates redox reactions, abolished the ameliorative effect of statins on mechanical nociceptive behavior. Additionally, the glutathione S-transferase inhibitor did not affect normal sensory perception or impair the anti-tumor effect of chemotherapy agents. A search for GST-associated molecules and pathways using artificial intelligence revealed that GST regulates inflammatory cytokines as a regulatory or causative gene. Our findings suggest that statins have class effects that ameliorate cytotoxic anti-cancer drug-induced mechanical allodynia via GST pathway activation.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105863"},"PeriodicalIF":4.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Mandukparni (Centella asiatica Linn Urban) in neurological disorders: Evidence from ethnopharmacology and clinical studies to network enrichment analysis","authors":"Ruchi Sharma ,&nbsp;Subhadip Banerjee ,&nbsp;Rohit Sharma","doi":"10.1016/j.neuint.2024.105865","DOIUrl":"10.1016/j.neuint.2024.105865","url":null,"abstract":"<div><div><em>Centella asiatica Linn</em> Urban (<em>C. asiatica</em>), aka <em>Mandukparni</em>, is one of the flagship herbs used in traditional medicines to effectively manage neurological problems. Although this plant has a wealth of comprehensive preclinical pharmacological profiles, further clinical research and execution of its molecular mode of action are still required. We searched electronic databases (Google Scholar, SciFinder, MEDLINE, Scopus, EMBASE, Science Direct, and PubMed) using relevant key words to retrieve information pertaining to <em>C. asiatica</em> till June 2023 and performed network pharmacology to understand the mechanism related to their neurobiological roles. This study extensively analyses its pharmacological properties, nutritional profile, ethnomedical uses, safety, and mechanistic role in treating neurological and neurodegenerative disorders. Additionally, a network pharmacology study was performed which suggests that its phytomolecules are involved in different neuroactive ligand-receptor pathways, glial cell differentiation, gliogenesis, and astrocyte differentiation. Hopefully, this report will lead to a paradigm shift in medical practice, research, and the creation of phytopharmaceuticals derived from <em>C. asiatica</em> that target the central nervous system.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105865"},"PeriodicalIF":4.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cycloleucine induces neural tube defects by reducing Pax3 expression and impairing the balance of proliferation and apoptosis in early neurulation","authors":"Li Zhang ,&nbsp;Dandan Li ,&nbsp;Yurong Liu ,&nbsp;Xiaona Zhang ,&nbsp;Kaixin Wei ,&nbsp;Xiaorong Zhao ,&nbsp;Huijing Ma ,&nbsp;Bo Niu ,&nbsp;Rui Cao ,&nbsp;Xiuwei Wang","doi":"10.1016/j.neuint.2024.105861","DOIUrl":"10.1016/j.neuint.2024.105861","url":null,"abstract":"<div><div>S-adenosylmethionine (SAM) plays a critical role in the development of neural tube defects (NTDs). Studies have shown that the paired box 3 (<em>Pax3</em>) gene is involved in neural tube closure. However, the exact mechanism between <em>Pax3</em> and NTDs induced by SAM deficiency remains unclear. Here, The NTD mouse model was induced using cycloleucine (CL), an inhibitor of SAM biosynthesis, to determine the effect of <em>Pax3</em> on NTDs. The effect of CL on NTD occurrence was assessed by 5-ethynyl-2′-deoxyuridine (EdU) staining, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and Western blot in NTD embryonic brain tissues and immortalized hippocampal neuron cells (HT-22). A high incidence of NTDs was observed when CL was administered at a dose of 200 mg/kg body weight. The levels of SAM and <em>Pax3</em> were significantly reduced in NTD embryonic brain tissues and HT-22 cells after CL exposure. Decreased proliferation and excessive apoptosis were observed in neuroepithelial cells of NTD embryos and HT-22 cells under SAM deficiency, but these effects were reversed by overexpression of <em>Pax3</em>. These results suggest that decreased expression of <em>Pax3</em> impairs the dynamic balance between cellular proliferation and apoptosis, contributing to NTDs induced by SAM deficiency, which would provide new insights for clarifying the underlying mechanism of NTDs.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105861"},"PeriodicalIF":4.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shh regulates M2 microglial polarization and fibrotic scar formation after ischemic stroke","authors":"Qinghuan Yang,&nbsp;Peiran Jiang,&nbsp;Hao Tang,&nbsp;Jun Wen,&nbsp;Li Zhou,&nbsp;Yong Zhao,&nbsp;Ling Wang,&nbsp;Jiani Wang,&nbsp;Qin Yang","doi":"10.1016/j.neuint.2024.105862","DOIUrl":"10.1016/j.neuint.2024.105862","url":null,"abstract":"<div><h3>Background</h3><div>Fibrotic scar formation is a critical pathological change impacting tissue reconstruction and functional recovery after ischemic stroke. The regulatory mechanisms behind fibrotic scarring in the central nervous system (CNS) remain largely unknown. While macrophages are known to play a role in fibrotic scar formation in peripheral tissues, the involvement of microglia, the resident immune cells of the CNS, in CNS fibrosis requires further exploration. The Sonic Hedgehog (Shh) signaling pathway, pivotal in embryonic development and tissue regeneration, is also crucial in modulating fibrosis in peripheral tissues. However, the impact and regulatory mechanisms of Shh on fibrotic scar formation post-ischemic stroke have not been thoroughly investigated.</div></div><div><h3>Methods</h3><div>This study explores whether Shh can regulate fibrotic scar formation post-ischemic stroke and its underlying mechanisms through in vivo and in vitro manipulation of Shh expression.</div></div><div><h3>Results</h3><div>Our results showed that Shh expression was upregulated in the serum of acute ischemic stroke patients, as well as in the serum, CSF, and ischemic regions of MCAO/R mice. Moreover, the upregulation of Shh expression was positively correlated with fibrotic scar formation and M2 microglial polarization. Shh knockdown inhibited fibrotic scar formation and M2 microglial polarization while aggravating neurological deficits in MCAO/R mice. In vitro, adenoviral knockdown or Smoothened Agonist (SAG) activation of Shh expression in BV2 cells following OGD/R regulated their polarization and influenced the expression of TGFβ1 and PDGFA, subsequently affecting fibroblast activation.</div></div><div><h3>Conclusion</h3><div>These results suggest that Shh regulates M2 microglial polarization and fibrotic scar formation after cerebral ischemia.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105862"},"PeriodicalIF":4.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}