Neurochemistry international最新文献

{"title":"Kaempferol promotes angiogenesis through HIF-1α/VEGF-A/Notch1 pathway in ischemic stroke rats","authors":"Sen Zhang ,&nbsp;Chengdi Liu ,&nbsp;Wan Li ,&nbsp;Yizhi Zhang ,&nbsp;Yihui Yang ,&nbsp;Hong Yang ,&nbsp;Ziyuan Zhao ,&nbsp;Fang Xu ,&nbsp;Wanxin Cao ,&nbsp;Xiaoxue Li ,&nbsp;Jinhua Wang ,&nbsp;Linglei Kong ,&nbsp;Guanhua Du","doi":"10.1016/j.neuint.2025.105953","DOIUrl":"10.1016/j.neuint.2025.105953","url":null,"abstract":"<div><div>Stroke is a severe disease characterized by the obstruction of blood vessels in the central nervous system. An essential therapeutic strategy for ischemic stroke is strengthening angiogenesis, which effectively promotes the long-term recovery of neurological function. Therefore, it is critical to explore and develop new drugs that promote angiogenesis after ischemic stroke. Kaempferol has been employed to treat ischemic diseases; However, its proangiogenic effects in ischemic stroke remain unclear. In the study, we explored the long-term therapeutic effects and mechanisms of kaempferol on ischemic stroke <em>in vivo</em> and <em>in vitro</em>. A rat model of autologous thrombus stroke and oxygen–glucose deprivation (OGD)-induced human brain microvascular endothelial cells (HBMECs) model was established to assess the effects of kaempferol <em>in vivo</em> (50 mg/kg/d, ig, 14 d) and <em>in vitro</em> (0.1, 0.3, 1 μmol L⁻¹). The results showed that long-term administration of kaempferol ameliorated neurological deficits and infarct volume in ischemic stroke rats. In addition, kaempferol relieved vascular embolization; enhanced microvascular endothelial cell survival, proliferation, migration, and lumen formation; increased the density of microvessels in the peri-infarct cortex; and promoted neovascular structure remodeling by increasing the coverage of astrocyte end-feet and expression of tight–junction proteins (TJPs). Further analysis revealed that the HIF-1α/VEGF-A/Notch1 signaling pathway was activated by kaempferol, and that inhibition of Notch1 blocked kaempferol-induced angiogenesis. Taken together, our results indicate that kaempferol exerts neuroprotective effects by stimulating endogenous angiogenesis and neovascular structural remodeling via the HIF-1α/VEGF-A/Notch1 signaling pathway, suggesting the therapeutic potential of kaempferol in ischemic stroke.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"185 ","pages":"Article 105953"},"PeriodicalIF":4.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481886","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":"Astrocyte-neuron metabolic crosstalk in ischaemic stroke","authors":"Zi-Lin Ren ,&nbsp;Xin Lan ,&nbsp;Jia-Lin Cheng ,&nbsp;Yu-Xiao Zheng ,&nbsp;Cong-Ai Chen ,&nbsp;Ying Liu ,&nbsp;Yan-Hui He ,&nbsp;Jin-Hua Han ,&nbsp;Qing-Guo Wang ,&nbsp;Fa-Feng Cheng ,&nbsp;Chang-Xiang Li ,&nbsp;Xue-Qian Wang","doi":"10.1016/j.neuint.2025.105954","DOIUrl":"10.1016/j.neuint.2025.105954","url":null,"abstract":"<div><div>Ischemic stroke (IS) is caused by temporary or permanent obstruction of the brain's blood supply. The disruption in glucose and oxygen delivery that results from the drop in blood flow impairs energy metabolism. A significant pathological feature of IS impaired energy metabolism. Astrocytes, as the most prevalent glial cells in the brain, sit in between neurons and the microvasculature. By taking advantage of their special anatomical location, they play a crucial part in regulating cerebral blood flow (CBF) and metabolism. Astrocytes can withstand hypoxic and ischemic conditions better than neurons do. Additionally, astrocytes are essential for maintaining the metabolism and function of neurons. Therefore, the \"neurocentric\" perspective on neuroenergetics is gradually giving way to a more comprehensive perspective that takes into account metabolic interaction between astrocytes and neurons. Since neurons in the core region of the infarct are unable to undergo oxidative metabolism, the focus of attention in this review is on neurons in the peri-infarct region. We'll go over the metabolic crosstalk of astrocytes and neurons during the acute phase of IS using three different types of metabolites: lactate, fatty acids (FAs), and amino acids, as well as the mitochondria. After IS, astrocytes in the peri-infarct zone can produce lactate, ketone bodies (KBs), glutamine (Gln), and <span>l</span>-serine, shuttling these metabolites, along with mitochondria, to neurons. This process helps maintain the energy requirements of neurons, preserves their redox state, and regulates neurotransmitter receptor activity.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"185 ","pages":"Article 105954"},"PeriodicalIF":4.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481884","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":"Dysregulation of immune system markers, gut microbiota and short-chain fatty acid production following prenatal alcohol exposure: A developmental perspective","authors":"Victoria R. Vella ,&nbsp;Garrett Ainsworth-Cruickshank ,&nbsp;Carolina Luft ,&nbsp;Kingston E. Wong ,&nbsp;Laura W. Parfrey ,&nbsp;A. Wayne Vogl ,&nbsp;Parker J. Holman ,&nbsp;Tamara S. Bodnar ,&nbsp;Charlis Raineki","doi":"10.1016/j.neuint.2025.105952","DOIUrl":"10.1016/j.neuint.2025.105952","url":null,"abstract":"<div><div>Prenatal alcohol exposure (PAE) can severely impact fetal development, including alterations to the developing immune system. Immune perturbations, in tandem with gut dysbiosis, have been linked to brain and behavioral dysfunction, but this relationship is poorly understood in the context of PAE. This study takes an ontogenetic approach to evaluate PAE-induced alterations to brain and serum cytokine levels and both the composition and metabolic output of the gut microbiota. Using a well-established rat model of PAE, cytokine levels in the serum, prefrontal cortex, amygdala, and hypothalamus as well as gut microbiota composition and short-chain fatty acid (SCFA) levels were assessed at three postnatal (P) timepoints: P8 (infancy), P22 (weaning), and P38 (adolescence). Male PAE rats had increased cytokine levels in the amygdala and hypothalamus, but not prefrontal cortex, at P8. This altered neuroimmune function was not seen in the PAE females. The effect of PAE on central cytokine levels was reduced at P22/38, the same age at which PAE-induced alterations in serum cytokine levels emerge in both sexes. PAE reduced bacterial diversity in both sexes at P8, but only in females at P38, where a PAE-induced unique community composition emerged. Both sexes had alterations to specific bacterial taxa (e.g., Firmicutes), some of which are important in producing the SCFA butyric acid, which was decreased in PAE animals at P22. These results demonstrate that PAE leads to sex- and age-specific alterations in immune function, gut microbiota and SCFA production, highlighting the need to consider both age and sex in future work.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"185 ","pages":"Article 105952"},"PeriodicalIF":4.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474875","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":"Reduction in presynaptic glutamate release and the prevention of glutamate excitotoxicity by lupeol in rats","authors":"Cheng-Wei Lu ,&nbsp;Tzu-Yu Lin ,&nbsp;Kun-Chieh Yeh ,&nbsp;Pei‐Wen Hsieh ,&nbsp;Kuan-Ming Chiu ,&nbsp;Ming-Yi Lee ,&nbsp;Su-Jane Wang","doi":"10.1016/j.neuint.2025.105951","DOIUrl":"10.1016/j.neuint.2025.105951","url":null,"abstract":"<div><div>This study aimed to investigate whether lupeol, a pentacyclic triterpenoid, affects glutamate release in isolated nerve terminals (synaptosomes) from the rat cerebral cortex and whether lupeol affects the excitotoxicity induced by kainic acid (KA) in rats. In rat cerebrocortical synaptosomes, lupeol reduced glutamate release in a manner that could be blocked by extracellular Ca²⁺-free medium or P/Q-type Ca²⁺ channel antagonism. The synaptosomal membrane potential was not affected by lupeol treatment. Docking data also revealed that lupeol formed a hydrogen bond with amino acid residues of the P/Q-type Ca²⁺ channel. In the KA-induced acute excitotoxicity model, lupeol pretreatment ameliorated cortical neurodegeneration and downregulated the expression of glutamate release-related proteins vesicular glutamate transporter 1 (VGLUT1) and phospho-synapsin I, thereby reducing the glutamate levels in the cortices of rats. Our findings suggest that lupeol may exert a neuroprotective effect by reducing glutamate excitotoxicity through the inhibition of presynaptic glutamate release. These results indicate that lupeol could be a promising candidate for the treatment of glutamatergic excitotoxicity and related neurological diseases.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"185 ","pages":"Article 105951"},"PeriodicalIF":4.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472084","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":"The novel peptide DBCH reduces LPS-stimulated NF-κB/MAPK signaling in BV-2 microglia and ameliorates cognitive impairment in scopolamine-treated mice by modulating BDNF/CREB","authors":"Ye-ji Yu ,&nbsp;Mujeeb Ur Rahman ,&nbsp;Rengasamy Balakrishnan ,&nbsp;Jong-Min Kim ,&nbsp;Jae Ho Kim ,&nbsp;Dong-Kug Choi","doi":"10.1016/j.neuint.2025.105946","DOIUrl":"10.1016/j.neuint.2025.105946","url":null,"abstract":"<div><div>Microglial-mediated neuroinflammation significantly impacts cognitive impairment, and modulating neuroinflammatory responses has emerged as a promising target for treatment. However, the specific role of microglial-mediated neuroinflammation in cognitive impairment associated with Alzheimer's disease (AD) remains unclear. In our continuous endeavors to seek potent anti-Alzheimer's agents, we recently synthesized and developed a series of peptidomimetic compounds, including dipeptide-68 bis-cyclohexylpropyl histidinamide (DBCH), derived from a caryopsis-1 peptide that has demonstrated anti-inflammatory and anti-microbial properties in various infectious diseases. Among the bioactive peptides synthesized, DBCH exhibited good neuroprotective and anti-inflammatory activity and high potency. Therefore, in this study, the neuroprotective and anti-inflammatory effects of DBCH were assessed in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and a scopolamine-induced C57BL/6 N amnesic mouse model. In the <em>in vitro</em> study, DBCH effectively suppressed the production and expression of nitric oxide (NO) and proinflammatory cytokines in BV-2 microglial cells stimulated with LPS. Furthermore, it effectively inhibited the LPS-triggered phosphorylation and activation of NF-κB/MAPK signaling and modulated inflammatory mediators, including iNOS and COX-2, in BV-2 microglial cells. <em>In vivo</em> results showed that DBCH administration of 5 or 10 mg/kg improved spatial memory learning and cognitive function in scopolamine-induced amnesic mice. Furthermore, DBCH treatment upregulated phosphorylated cAMP-response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) levels and downregulated the inflammatory response. Overall, DBCH effectively prevented both scopolamine-induced cognitive impairment and neuroinflammation. Our research findings suggest that DBCH may serve as a medication for cognitive decline associated with AD.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"185 ","pages":"Article 105946"},"PeriodicalIF":4.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456385","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":"Vagus nerve stimulation inhibits PANoptosis and promotes neurofunctional recovery of cerebral ischemic stroke in a Sirt1-dependent manner","authors":"Hao Tang ,&nbsp;Jun Wen ,&nbsp;Ling Wang ,&nbsp;Qinghuan Yang ,&nbsp;Ting Qin ,&nbsp;Yu Ren ,&nbsp;Yong Zhao ,&nbsp;Changqing Li ,&nbsp;Jiani Li ,&nbsp;Hui Cao ,&nbsp;Jianfeng Xu ,&nbsp;Qin Yang","doi":"10.1016/j.neuint.2025.105950","DOIUrl":"10.1016/j.neuint.2025.105950","url":null,"abstract":"<div><div>Vagus nerve stimulation (VNS) can promote neurofunctional recovery following cerebral ischemic stroke (CIS), but the underlying mechanism remains unclear. PANoptosis, a novel form of inflammatory programmed cell death, may play a role in the progression of CIS. Our previous studies have indicated that Sirt1 exerts neuroprotection against CIS by modulating various programmed cell death pathways. It needs to be clarified whether and how VNS regulates PANoptosis through Sirt1, thereby affecting the recovery of CIS. This study aims to clarify the role of VNS in modulating neuronal PANoptosis following CIS, and elucidate its underlying mechanisms. Models of middle cerebral artery occlusion/reperfusion (MCAO/R) in rats and oxygen-glucose deprivation/reoxygenation (OGD/R) in primary neurons were established to assess the occurrence of neuronal PANoptosis following CIS. Circulating Sirt1 levels were measured in two independent cohorts of acute ischemic stroke (AIS) patients. VNS was administered to activate Sirt1, and its effects on PANoptosis and neurological recovery were evaluated. We found that neuronal PANoptosis was induced following CIS, which was reversed via VNS intervention. Sirt1 levels in serum of AIS patients were significantly increased, and positively correlated with infarct volume and National Institutes of Health Stroke Scale scores. In contrast, Sirt1 was downregulated in brain tissue from rodent models and AIS patients. This discrepancy in expression levels can be attributed to the increased generation of Sirt1 by peripheral macrophages. VNS upregulated Sirt1 expression, while the Sirt1 inhibitor EX527 negated the effects of VNS on PANoptosis, infarct volume, and neurofunctional recovery. These findings indicate that VNS may inhibit PANoptosis and promote neurofunctional recovery following CIS in a Sirt1-dependent manner, which may be a new potential target for stroke therapy. Sirt1 may also serve as a blood biomarker for patient stratification with independent prognostic value in AIS patients.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"184 ","pages":"Article 105950"},"PeriodicalIF":4.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436682","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":"Beyond plaques and tangles: The role of immune cell dysfunction in Alzheimer's disease","authors":"Nasif Hussain ,&nbsp;Mohd Moin Khan ,&nbsp;Ayushi Sharma ,&nbsp;Rakesh K. Singh ,&nbsp;Rizwan Hasan Khan","doi":"10.1016/j.neuint.2025.105947","DOIUrl":"10.1016/j.neuint.2025.105947","url":null,"abstract":"<div><div>The interplay between immune cell dysfunction and associated neuroinflammation plays a critical role in the pathogenesis of Alzheimer's disease. Neuroinflammation, orchestrated by microglia and peripheral immune cells, exacerbates synaptic dysfunction and neurodegeneration in AD. Emerging evidence suggests a systemic immune response in AD, challenging traditional views of neurocentric pathology. Therapeutic strategies targeting neuroinflammation hold promise, yet translating preclinical findings into clinical success remains elusive. This article presents recent advances in AD scientific studies, highlighting the pivotal role of immune cell dysfunction and signaling pathways in disease progression. We also discussed therapeutic studies targeting immune cell dysregulation, as treatment methods. This advocates for a paradigm shift towards holistic approaches that integrate peripheral and central immune responses, fostering a comprehensive understanding of AD pathophysiology and paving the way for transformative interventions.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"184 ","pages":"Article 105947"},"PeriodicalIF":4.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143430226","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":"Neuro-nutraceuticals: Emerging molecular and functional insights into how natural products improve brain health","authors":"K.P. Mohanakumar (Director, Professor of Biological Sciences) ,&nbsp;Catarina Rendeiro (Assistant Professor in Nutritional Sciences) ,&nbsp;Philip M. Beart (formerly Professor)","doi":"10.1016/j.neuint.2025.105948","DOIUrl":"10.1016/j.neuint.2025.105948","url":null,"abstract":"<div><div>The editors in assembling this Special Issue, “Neuro-nutraceuticals: Emerging Molecular and Functional Insights into how Natural Products Improve Brain Health”, sought to advance our understanding of how such chemical entities alone or in group maintain brain metabolism and homeostasis so that neurons, glia and endothelial cells are healthy during development, ageing and in neuropathologies. The growth of interest in neuro-nutraceuticals and all aspects of their actions relevant to the health of the nervous system continues to amaze all. This Special Issue # 4 contains 39 articles, and we sought to highlight in this Special Issue important new advances and key issues pertinent to future clinical application of neuro-nutraceuticals. The diversity of topics covered is quite broad and includes significant articles on enteric microbiome and brain health. The Editors have tried to provide an up-to-date account of how nutraceuticals work at the molecular and cellular level, and what are the known molecular targets that ultimately can be leveraged clinically to enable the brain to function better. With respect to brain ailments and treatments, single molecule effects, and a therapeutic group of molecules from dietary herbals are discussed in this Special Issue.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"185 ","pages":"Article 105948"},"PeriodicalIF":4.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424638","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":"Temporal and spatial expression of Phosphodiesterase-4B after sciatic nerve compression in rats and its mechanism of action on sciatic nerve repair","authors":"Yufei Wang ,&nbsp;Youfei Zhou ,&nbsp;Jinhao Liu ,&nbsp;Chen Liu ,&nbsp;Zirui Li ,&nbsp;Xuehua Sun","doi":"10.1016/j.neuint.2025.105940","DOIUrl":"10.1016/j.neuint.2025.105940","url":null,"abstract":"<div><h3>Background</h3><div>Macrophage phenotype transformation is vital in sciatic nerve injury. The study of biomolecule expression and its impact on macrophage phenotype transformation is a current research focus.</div></div><div><h3>Material and methods</h3><div>We created a rat model of sciatic nerve compression injury to examine the expression of PDE4B and the distribution of M1 and M2 macrophages over time and their relationship. We confirmed the effect of inhibiting PDE4B expression on macrophage phenotype changes and its role in sciatic nerve injury repair. The experiments consisted of immunofluorescence, western blotting, HE staining, TEM, and behavioral evaluation. Investigate in vivo experiment results with RAW264.7 cells in vitro. PDE4B knockdown lentivirus was transfected into RAW264.7 cells and stimulated with LPS and IFN-γ. We assessed CD86 and CD206 expression using flow cytometry and western blot. The relationship between PDE4B and the TLR4/NF-κB pathway was studied.</div></div><div><h3>Results</h3><div>PDE4B peaked on day 7 after surgery, alongside the highest M1 macrophages count. PDE4B and M1 macrophages decreased, and M2 macrophages increased. PDE4B inhibition reduced M1 macrophages, increased M2 macrophages, suppressed inflammation, and promoted sciatic nerve repair while alleviating pain. In vitro experiments confirmed that PDE4B regulated macrophage phenotype via the TLR4/NF-κB pathway. Inhibiting PDE4B disrupted this pathway and promoted M2 macrophage transformation.</div></div><div><h3>Conclusions</h3><div>In the sciatic nerve injury, PDE4B expression is linked to the M1 macrophage phenotype. Low PDE4B expression facilitates the M1 to M2 macrophage transformation and supports sciatic nerve repair. The TLR4/NF-κB pathway is involved in this process.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"185 ","pages":"Article 105940"},"PeriodicalIF":4.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363500","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":"Cerebellum KCC2 protein expression plasticity in response to cerebral cortical stroke","authors":"Shamseldin Metwally ,&nbsp;Okan Capuk ,&nbsp;Jun Wang ,&nbsp;Mohammad Iqbal H. Bhuiyan ,&nbsp;Qiang Li ,&nbsp;Kathiravan Kaliyappan ,&nbsp;Bo Chen ,&nbsp;Daryl Fields ,&nbsp;Dandan Sun","doi":"10.1016/j.neuint.2025.105939","DOIUrl":"10.1016/j.neuint.2025.105939","url":null,"abstract":"<div><h3>Background</h3><div>Recent evidence suggests extra-cortical adaptations within the cerebellum may contribute to motor recovery in patients with cortical ischemic strokes. The molecular/cellular adaptations enabling this effect to have not been identified. Chloride transport proteins (NKCC1 and KCC2) are important regulators of neuronal transmission and may underlie adaptive changes following ischemic stroke.</div></div><div><h3>Objective</h3><div>Examine changes in cerebellar NKCC1 and KCC2 protein expression following cortical ischemic stroke.</div></div><div><h3>Methods</h3><div>Adult C57BL/6J male mice underwent sham or the left middle cerebral artery occlusion (tMCAo)-induced ischemic stroke. Changes of NKCC1 and KCC2 proteins within the deep cerebellar nuclei (DCN) were assessed by immunofluorescence staining.</div></div><div><h3>Results</h3><div>tMCAo induced selective infarct lesion in the left striatum and cortex of the stroke mice but not in other brain regions including cerebellum. The inwardly directed chloride transporter NKCC1 was equivocally expressed within bi-hemispheric DCN of both sham control and stroke mice. In contrast, the outwardly directed chloride transporter KCC2 protein expression was significantly higher in the bi-hemispheric DCN of stroke brains, compared to sham controls. Double immunostaining analysis revealed a statistically significant increase in KCC2 intensity within VGLUT-1⁺ neurons of the ipsilateral DCN of the stroke mice, but not in the VGAT⁺ neurons.</div></div><div><h3>Conclusions</h3><div>Ischemic cortical stroke stimulates KCC2 protein expression in the DCN VGLUT-1⁺ neurons, without a change in NKCC1 protein expression.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"184 ","pages":"Article 105939"},"PeriodicalIF":4.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254027","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}