Neuroscience Letters最新文献_第6页

Constraint-induced movement therapy combined with Nogo-A downregulation enhances corticospinal tract remodeling and motor function in hemiplegic cerebral palsy mice 约束运动疗法联合Nogo-A下调可增强偏瘫脑瘫小鼠皮质脊髓束重构和运动功能。

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-01-01 Epub Date: 2025-11-15 DOI: 10.1016/j.neulet.2025.138447

Yuan Huang , Yunlan Xie , Liru Liu , Danxia Fan , Wen Le , Xiaoying Zhang , Tingting Peng , Wenhui Li , Huijuan Lin , Lu He , Hongmei Tang , Kaishou Xu

{"title":"Constraint-induced movement therapy combined with Nogo-A downregulation enhances corticospinal tract remodeling and motor function in hemiplegic cerebral palsy mice","authors":"Yuan Huang , Yunlan Xie , Liru Liu , Danxia Fan , Wen Le , Xiaoying Zhang , Tingting Peng , Wenhui Li , Huijuan Lin , Lu He , Hongmei Tang , Kaishou Xu","doi":"10.1016/j.neulet.2025.138447","DOIUrl":"10.1016/j.neulet.2025.138447","url":null,"abstract":"<div><div>Constraint-induced movement therapy (CIMT) enhances hand function in hemiplegic cerebral palsy (HCP) and stroke, partly by strengthening corticospinal tract (CST) projections, while down-regulated Nogo-A has been shown to facilitate neural regeneration in stroke and multiple sclerosis. However, their combined therapeutic effect remains unclear. Therefore, this study explored the impact of CIMT combined with Nogo-A downregulation on CST remodeling and motor function in HCP mice. Mice were randomly assigned to five groups: control, HCP, HCP + CIMT, HCP + SN (siRNA-Nogo-A treatment) and HCP + SN + CIMT. Rotarod and grip test were performed to assess the motor function. Western blot and immunofluorescence staining were performed to quantify Nogo-A and PKCγ expression in the M1 region. Diffusion tensor imaging and transmission electron microscopy were applied to assess fractional anisotropy (FA) of CST and myelin remodeling. Compared with controls, the HCP group exhibited significant motor dysfunction and myelin impairment, characterized by increased Nogo-A expression, decreased PKCγ expression, and reduced FA value of CST (<em>p</em> < 0.05). In contrast, mice treated with CIMT or SN exhibited improved motor function, reduced Nogo-A expression, elevated PKCγ expression, increased FA value of CST, and enhanced myelin remodeling compared with the HCP group (<em>p</em> < 0.05). Notably, CIMT and SN exerted synergistic effects, as the HCP + SN + CIMT group outperformed either single-treatment group (<em>p</em> < 0.05). These findings suggest CIMT combined with Nogo-A downregulation synergistically enhances motor function in HCP mice by reducing Nogo-A expression in M1 region and promoting CST remodeling.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"870 ","pages":"Article 138447"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145541633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuro-protection of swertisin against impairment induced by Aβ25-35 by acting on COX-2 to up-regulate 2-AG and suppressing neuroinflammation 獐牙菜素通过作用于COX-2上调2-AG和抑制神经炎症对Aβ25-35损伤的神经保护作用

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-01-01 Epub Date: 2025-10-28 DOI: 10.1016/j.neulet.2025.138429

Jiang Wu , Lijin Zhou , Chao Lang

{"title":"Neuro-protection of swertisin against impairment induced by Aβ25-35 by acting on COX-2 to up-regulate 2-AG and suppressing neuroinflammation","authors":"Jiang Wu , Lijin Zhou , Chao Lang","doi":"10.1016/j.neulet.2025.138429","DOIUrl":"10.1016/j.neulet.2025.138429","url":null,"abstract":"<div><div>Ziziphi Spinosae Semen (Suan Zao Ren) is a traditional Chinese medicine with the functions of nourishing the heart and liver, calming the mind, and stopping sweating. Swertisin, one of the main active ingredients in Ziziphi Spinosae Semen, has a wide range of pharmacological effects such as anti-inflammation, anti-oxidation, and enhancement of learning and memory. Based on the Aβ cascade and the neuroinflammatory theory, combined with the anti-inflammatory neuroprotective effect of endocannabinoid 2-AG, this work integrated modern biochemical technology methods such as liquid chromatography-mass spectrometry, Western blot, and electrophysiological technique to explore the neuroprotective effects and potential mechanism of swertisin on the Alzheimer’s disease (AD) model induced by Aβ<sub>25-35</sub>. The results showed that swertisin relieved impairment of learning and memory caused by Aβ<sub>25-35</sub> on hippocampus slice by decreasing COX-2 expression and inhibiting COX-2 activity to up-regulate the endogenous 2-AG, and suppressing neuroinflammation and neuronal apoptosis <em>via</em> CB1R-dependent NF-κB pathway. It was further discovered that swertisin protected the primary hippocampal neurons, reduced over-expression of COX-2, and relieved the neuroinflammatory against Aβ<sub>25-35</sub> through the CB1R-dependent NF-κB signaling pathway. Finally, it was confirmed that swertisin alleviated BV-2 cell apoptosis induced by Aβ<sub>25-35.</sub> These results help us understand the mechanism of swertisin against AD and promote the development of related drugs and healthy products.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"870 ","pages":"Article 138429"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145409674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Environmental enrichment prevents depression-like behaviours induced by immune system activation in male mice 环境富集可防止雄性小鼠免疫系统激活引起的抑郁样行为。

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-01-01 Epub Date: 2025-11-13 DOI: 10.1016/j.neulet.2025.138450

Alexandre Kanashiro , Priscila Medeiros , Ana Carolina Medeiros , Frederico Rogério Ferreira , Alline Cristina de Campos , Tatiana Barichello , Norberto Cysne Coimbra

{"title":"Environmental enrichment prevents depression-like behaviours induced by immune system activation in male mice","authors":"Alexandre Kanashiro , Priscila Medeiros , Ana Carolina Medeiros , Frederico Rogério Ferreira , Alline Cristina de Campos , Tatiana Barichello , Norberto Cysne Coimbra","doi":"10.1016/j.neulet.2025.138450","DOIUrl":"10.1016/j.neulet.2025.138450","url":null,"abstract":"<div><div>Depression is a debilitating psychiatric illness, and its etiology as well as resistance to current pharmacological treatments are increasingly associated with low-grade inflammation. Environmental enrichment (EE), a paradigm that combines sensory and cognitive stimulation, social interaction, and voluntary physical activity, has been widely used to alleviate depression-like behaviours in rodent models, focusing on exposure to psychosocial stressors. However, the potential benefits of EE against depression-like behaviours triggered by immune activation remain unexplored. In this study, male C57BL/6 mice were housed under standard conditions or in EE. After six weeks, mice received an intraperitoneal injection of either physiological saline (vehicle) or lipopolysaccharide (LPS), a potent immunologic stimulus. Twenty-four hours later, anhedonia and behavioural despair were evaluated using the tail suspension test (i.e., frequency, latency, and time of immobility) and the splash test (i.e., latency, frequency, and time of grooming), respectively. LPS administration induced behavioural alterations consistent with depression-like behaviours characterised by increased immobility and decreased grooming. Remarkably, EE exposure prevented the development of LPS-induced depression-like behaviours in the tail suspension test and improved specific parameters in the splash test. Taken together, these findings highlight the therapeutic potential of EE as a non-pharmacological strategy for preventing or alleviating immune system activation-associated depression.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"870 ","pages":"Article 138450"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sensory afferents in the mammary papilla are eliminated during the lactation 乳突中的感觉传入在哺乳期被消除。

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-01-01 Epub Date: 2025-11-04 DOI: 10.1016/j.neulet.2025.138441

Kei Nakayama , Kotoko Suzuki , Yukiko Marunaka , Mari Kondo , Yuji Yokouchi , Naoki Takeda , Kenichi Yamamura , Hiroshi Hasegawa

引用次数: 0

Immunohistochemically-detected differential localization of CXCL14 in mouse cerebellum suggesting the presence of neuronal and glial forms of CXCL14 免疫组织化学检测小鼠小脑中CXCL14的差异定位提示CXCL14存在神经元和胶质形式。

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-01-01 Epub Date: 2025-11-07 DOI: 10.1016/j.neulet.2025.138442

Hirohumi Suzuki , Toshiharu Yamamoto , Aya Hasegawa , Toru Tamaki , Jun-ya Komagata , Takayoshi Yamaga , Tetsu Akasaka , Ryu-ichiro Hata

{"title":"Immunohistochemically-detected differential localization of CXCL14 in mouse cerebellum suggesting the presence of neuronal and glial forms of CXCL14","authors":"Hirohumi Suzuki , Toshiharu Yamamoto , Aya Hasegawa , Toru Tamaki , Jun-ya Komagata , Takayoshi Yamaga , Tetsu Akasaka , Ryu-ichiro Hata","doi":"10.1016/j.neulet.2025.138442","DOIUrl":"10.1016/j.neulet.2025.138442","url":null,"abstract":"<div><div>In this study we compared staining profiles in mouse cerebellum, using two anti-CXCL14 antibodies, which we designated α and β. The α anti-CXCL14 antibody labeled Purkinje neurons; this was confirmed by double-immunofluorescence staining with calbindin D-28k, a marker for Purkinje neurons. The β anti-CXCL14 antibody marked Bergmann glia; this was confirmed by combinational staining with glial fibrillary acidic protein, a marker for Bergmann glia. Both staining profiles were abolished by preabsorption of each antibody with recombinant human CXCL14. Western blot analyses using these two antibodies indicated that they both recognized recombinant human and mouse CXCL14s, which migrated at approximately a 12 kDa position. Furthermore, the α anti-CXCL14 antibody labeled major bands at approximately 15 kDa and 21 kDa, and a minor band at approximately 19 kDa from a Triton-X fraction of mouse cerebellum. However, there were no immunostaining bands from a Tris-HCl fraction. In contrast, the β anti-CXCL14 antibody labeled a band of approximately 18 kDa from a Tris-HCl fraction of cerebellum, but no immunoreactive bands were detected from a Triton-X fraction. These results suggest that mouse cerebellum has at least two forms of CXCL14; presumably a neuronal form and a glial form.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"870 ","pages":"Article 138442"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Involvement of CXCR2 in chronic postsurgical pain occurrence through ERK/p38 activation CXCR2通过ERK/p38激活参与慢性术后疼痛的发生。

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-01-01 Epub Date: 2025-11-03 DOI: 10.1016/j.neulet.2025.138440

TianYu Ge , Xi Chen , Chang Liu , SaiSai Huang

{"title":"Involvement of CXCR2 in chronic postsurgical pain occurrence through ERK/p38 activation","authors":"TianYu Ge , Xi Chen , Chang Liu , SaiSai Huang","doi":"10.1016/j.neulet.2025.138440","DOIUrl":"10.1016/j.neulet.2025.138440","url":null,"abstract":"<div><div>Chronic postsurgical pain (CPSP) is a global concern associated with significant health and economic issues for patients. We investigated the effects of C-X-C motif chemokine receptor 2 (CXCR2) related signal transduction mechanisms on CPSP in a rat skin muscle incision and retraction (SMIR) model. Following model establishment, glial cells in the spinal dorsal horn were activated, and the expression of inflammatory factors (tumor necrosis factor (TNF)-α and interleukin (IL)-1β increased. The SMIR group demonstrated elevated expression of CXCR2, phosphorylated ERK (p-ERK), and phosphorylated p38 (p-p38) in the spinal dorsal horn. After intrathecal injection of the CXCR2 antagonist SB225002, the rats’ pain threshold increased, accompanied by reduced expression of inflammatory factors and reversal of glial cell activation. Additionally, primary microglial cells induced by lipopolysaccharide were used as an in vitro model. Transfection with si-CXCR2 led to decreased expression of p-ERK and p-p38 in microglial cells, along with lower TNF-α and IL-1β levels in the cell supernatant. These results indicate that CXCR2 activates spinal glial cells via the ERK/p38 pathway, promoting neuroinflammation, and CPSP, whereas CXCR2 inhibition counteracts these effects and alleviates CPSP.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"870 ","pages":"Article 138440"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Artemisinin attenuates quinolinic acid-induced neurotoxicity by suppressing neuroinflammatory and apoptotic gene expression in rats 青蒿素通过抑制大鼠神经炎症和凋亡基因表达来减轻喹啉酸诱导的神经毒性。

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-01-01 Epub Date: 2025-11-13 DOI: 10.1016/j.neulet.2025.138449

Richmond Arthur , Uma Shanker , Manjinder Singh , Thakur Gurjeet Singh , Puneet Kumar

{"title":"Artemisinin attenuates quinolinic acid-induced neurotoxicity by suppressing neuroinflammatory and apoptotic gene expression in rats","authors":"Richmond Arthur , Uma Shanker , Manjinder Singh , Thakur Gurjeet Singh , Puneet Kumar","doi":"10.1016/j.neulet.2025.138449","DOIUrl":"10.1016/j.neulet.2025.138449","url":null,"abstract":"<div><div>Neurotoxicity, characterised by the structural and functional disruption of the nervous system, remains a major contributor to the pathophysiology of neurodegenerative disorders. It is mostly caused by oxidative stress, excitotoxicity, mitochondrial dysfunction, and neuroinflammation, which results in gradual neuronal damage and death. Despite breakthroughs in understanding its underlying principles, effective therapeutic strategies to alleviate neurotoxic harm are still limited. Beyond its antimalarial action, artemisinin, a sesquiterpene lactone obtained from <em>Artemisia annua</em>, has recently attracted attention for its strong anti-inflammatory, antioxidant, and neuroprotective qualities. QA was bilaterally injected directly into the rat striatum to simulate neurotoxic conditions, followed by a 21-day artemisinin treatment. On days 0, 14, and 21, motor coordination was evaluated through behavioural assessments, including narrow beam walking, the open field test, and rotarod performance. Striatal homogenates were tested for oxidative stress parameters. qRT-PCR was used for molecular investigations. Hematoxylin and eosin staining was used to investigate histopathological changes in the striatum. Results indicated that artemisinin mitigated neurotoxicity in the experimental rats. It reduced oxidative stress and inflammatory and apoptotic markers in striatal homogenates. In conclusion, artemisinin efficiently reduced neurotoxic damage, indicating its promise as a potential neuroprotective alternative for neurodegenerative diseases.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"870 ","pages":"Article 138449"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expression of serotonin transporter (SERT) and receptors 5-HTR1A and 5-HTR2A in an animal model of hypothermia 低温动物模型中血清素转运体（SERT）和受体5-HTR1A和5-HTR2A的表达

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-01-01 Epub Date: 2025-11-11 DOI: 10.1016/j.neulet.2025.138448

Andrei Negoiţă , Bogdan Amuzescu , Dan Florin Mihăilescu , Daniel Dumitru Banciu , Adela Banciu

{"title":"Expression of serotonin transporter (SERT) and receptors 5-HTR1A and 5-HTR2A in an animal model of hypothermia","authors":"Andrei Negoiţă , Bogdan Amuzescu , Dan Florin Mihăilescu , Daniel Dumitru Banciu , Adela Banciu","doi":"10.1016/j.neulet.2025.138448","DOIUrl":"10.1016/j.neulet.2025.138448","url":null,"abstract":"<div><div>The role of anterior hypothalamus and preoptic area in thermoregulation has been studied since the late 19<sup>th</sup> century (Charles Richet 1884, Aronsohn&Sachs 1885), and thermosensitive neurons have been recorded in these areas. Numerous animal studies with injection of serotonergic agonists or antagonists proved activation of thermoregulatory responses, and complex serotonergic circuits with origin in dorsal raphe nucleus (DRN) and projection in hypothalamus and preoptic area (POA), nucleus accumbens (Acc), and central amygdala were identified. We assessed the expression of serotonin transporter SERT, 5-HT1A and 5-HT2A receptors at mRNA and protein level in several brain regions: brainstem raphe, hypothalamus, Acc and POA, amygdala, piriform cortex (Pir) in adult male CD1 mice kept 4 h/day at 4 °C or normal temperature (control) for 1–2 months. For qRT-PCR total RNA was extracted from fresh samples with a GenElute™ kit (Sigma), followed by RT and qPCR with hydrolysis probes (Applied Biosystems). For immunofluorescence 200 µm slices were cut from fixed brains and stained with primary antibodies ASR-021, ASR-033, AMT-004 (Alomone Labs) and secondary antibody N2404-Ab635P-L (NanoTag), co-stained with phalloidin-AlexaFluor488 and DAPI. We obtained statistically significant (two-tailed <em>t</em> test) increases in mRNA expression in hypothermia vs. control for SERT and 5-HT2A in the brainstem raphe and hypothalamus. Fluorescence intensities (averaged over small relevant regions and normalized to DAPI fluorescence) were higher in hypothermia for the two receptors in DRN and Acc, and similar to control levels in Pir and amygdala, proving activation of central serotonergic thermoregulatory circuits.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"870 ","pages":"Article 138448"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intermittent mild skin cooling stimulation inhibits pineal melatonin secretion in urethane-anesthetized rats 间歇性轻度皮肤降温刺激抑制聚氨酯麻醉大鼠松果体褪黑素分泌。

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-01-01 Epub Date: 2025-11-12 DOI: 10.1016/j.neulet.2025.138444

Nobuhiro Watanabe, Masamichi Moriya, Harumi Hotta

{"title":"Intermittent mild skin cooling stimulation inhibits pineal melatonin secretion in urethane-anesthetized rats","authors":"Nobuhiro Watanabe, Masamichi Moriya, Harumi Hotta","doi":"10.1016/j.neulet.2025.138444","DOIUrl":"10.1016/j.neulet.2025.138444","url":null,"abstract":"<div><div>Skin thermal stimulation can induce reflexive autonomic nerve responses and thereby influence endocrine functions. Melatonin, secreted from the pineal gland primarily under sympathetic control, exerts various physiological functions including sleep–wake rhythm regulation. Although photostimulation is a well-known regulator of melatonin secretion, the effect of skin thermal stimulation remains unclear. In this study, we investigated whether intermittent mild cooling stimulation of the skin alters melatonin secretion from the pineal gland in urethane-anesthetized rats. Animals were artificially ventilated, and their rectal temperatures were maintained using a heating pad and a lamp. Using <em>in vivo</em> microdialysis, pineal perfusate was collected every 20 min for 100 min during the animal’s light phase and the melatonin concentrations were measured via ELISA. Intermittent cooling stimulation was applied to the skin of the trunk using a Peltier-based contact thermode by alternating the temperature between 30 °C and 15 °C (15 °C/s) for 20 min. Without cooling stimulation, the melatonin concentration in the pineal perfusate remained stable for 100 min. Cooling stimulation did not affect the melatonin concentration during application but reduced it for 40 min after the stimulation was discontinued. This suppression was abolished in rats with bilateral cervical sympathetic nerve transection. Our findings suggest that intermittent mild skin cooling stimulation reflexively suppresses pineal melatonin secretion through cervical sympathetic nerves.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"870 ","pages":"Article 138444"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Limited effects of the REV-ERB agonist SR9009 after mouse spinal cord contusion: Reduced acute pathology with unaffected functional recovery and chronic white matter loss REV-ERB激动剂SR9009在小鼠脊髓挫伤后的有限作用：减少急性病理，未受影响的功能恢复和慢性白质损失。

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-01-01 Epub Date: 2025-11-12 DOI: 10.1016/j.neulet.2025.138443

Lukasz P. Slomnicki , Emily Hodges , Christine Armstrong , Johnny Morehouse , Darlene Burke , Sujata Saraswat Ohri , Thomas P. Burris , Michal Hetman

{"title":"Limited effects of the REV-ERB agonist SR9009 after mouse spinal cord contusion: Reduced acute pathology with unaffected functional recovery and chronic white matter loss","authors":"Lukasz P. Slomnicki , Emily Hodges , Christine Armstrong , Johnny Morehouse , Darlene Burke , Sujata Saraswat Ohri , Thomas P. Burris , Michal Hetman","doi":"10.1016/j.neulet.2025.138443","DOIUrl":"10.1016/j.neulet.2025.138443","url":null,"abstract":"<div><div>The ligand-regulated transcription factors REV-ERBα/NR1D1 and REV-ERBβ/NR1D2 are promising neuroprotective targets. Systemic administration of the REV-ERB agonist SR9009 has been shown to reduce neuroinflammation, limit tissue loss, and enhance functional recovery in several models of acute CNS injury. To evaluate its potential in spinal cord injury (SCI), a moderate contusion was induced at the T9 level in mice. SR9009 was administered intraperitoneally at 100 mg/kg per day (two 50 mg/kg doses at ZT1 and ZT12) for the first 7 days post-injury, when tissue damage is most pronounced in this model. At 3 days post-SCI, SR9009-treated mice exhibited reduced hematoma and decreased expression of transcripts associated with blood–spinal cord barrier disruption, inflammation, and cellular stress responses. However, hindlimb functional recovery remained unchanged throughout 6 weeks of follow-up, and no significant differences in white matter sparing were observed at study completion. These findings indicate that although SR9009 reduces acute activation of some secondary injury cascades, it does not promote long-term tissue preservation or functional recovery after contusive SCI in mice.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"870 ","pages":"Article 138443"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0