Experimental Neurology最新文献

{"title":"Crosstalk between lipocalin-2 and IL-6 in traumatic brain injury: Closely related biomarkers","authors":"Jae-Hong Kim ,&nbsp;Han-Gil Jeong ,&nbsp;Seung Jae Hyeon ,&nbsp;Uiyeol Park ,&nbsp;Won-Jong Oh ,&nbsp;Junmo Hwang ,&nbsp;Hyun-Ho Lim ,&nbsp;Pan-Woo Ko ,&nbsp;Ho-Won Lee ,&nbsp;Won-Ha Lee ,&nbsp;Hoon Ryu ,&nbsp;Kyoungho Suk","doi":"10.1016/j.expneurol.2024.115092","DOIUrl":"10.1016/j.expneurol.2024.115092","url":null,"abstract":"<div><div>Clinical biomarkers are crucial for diagnosing and predicting outcomes in patients with traumatic brain injury (TBI). In this study, we performed an unbiased analysis of plasma proteins in acute TBI patients using bead-based multiplex assays and identified a strong positive correlation between LCN2 and IL-6 levels. Based on these findings, we hypothesized that LCN2 and IL-6 are closely related circulating biomarkers for TBI. Our previous and current studies demonstrate that the expression of LCN2, IL-6, and its receptors is upregulated in patients with chronic traumatic encephalopathy, in mouse models of traumatic and ischemic injury, and in an <em>in vitro</em> scratch injury model. <em>Lcn2</em>-deficiency reduced the injury-induced expression of IL-6 and its receptors in both animal and scratch injury models. These results suggest an augmented LCN2-dependent IL-6 signaling in the injured brain. As both LCN2 and IL-6 are secreted proinflammatory mediators, we further explored the possibility of cross-regulation between LCN2 and IL-6. In cultured glial cells, treatment with recombinant LCN2 protein enhanced the microglial expression of IL-6, while IL-6 protein treatment increased astrocytic LCN2 expression. Moreover, IL-6 expression and release were elevated in LCN2-overexpressing transgenic mice. Mechanistically, IL-6 enhanced astrocytic LCN2 expression through STAT3 signaling, while LCN2 upregulated microglial IL-6 expression through the NF-κB pathway. Taken together, our results suggest an important role of the LCN2-IL-6 axis in amplifying neuroinflammation through a positive feedback loop in secondary brain injury conditions. Finally, this study implies the utility of LCN2 and IL-6 as closely related biomarkers for TBI diagnosis and prognosis.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"385 ","pages":"Article 115092"},"PeriodicalIF":4.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785020","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":"Mitigating mitochondrial dysfunction and neuroinflammation by hematoma aspiration in a new surgical model for severe intracerebral hemorrhage","authors":"Wei-Fen Hu ,&nbsp;Chien-Hui Lee ,&nbsp;Cheng-Yoong Pang ,&nbsp;Hsin-Yi Huang ,&nbsp;Sheng-Tzung Tsai ,&nbsp;Po-Kai Wang ,&nbsp;Mu-Ting Shih ,&nbsp;Pei-Ying Cheah ,&nbsp;Yi-Feng Wu ,&nbsp;Andy Po-Yi Tsai ,&nbsp;Kuan-Yin Tseng ,&nbsp;Mikko Airavaara ,&nbsp;Hock-Kean Liew","doi":"10.1016/j.expneurol.2024.115098","DOIUrl":"10.1016/j.expneurol.2024.115098","url":null,"abstract":"<div><h3>Background</h3><div>Intracerebral hemorrhage (ICH) is associated with a large hematoma that causes compression, increased intracranial pressure (IICP), midline shift, and brain herniation, and may ultimately lead to death. Urgent surgical removal of the large hematoma can ameliorate these injuries, which would be life-saving, but has not improved clinical outcome. A suitable animal model that mimics the clinically relevant human severe ICH injury requiring surgical hematoma evacuation is urgently needed. Here, we established a novel model of severe ICH in rats allowing aspiration of the hematoma and studying the effects of mitochondrial dysfunction in ICH.</div></div><div><h3>Methods</h3><div>Severe ICH was induced by intra-striatal injection of 0.6 U of collagenase in 3 μL sterile saline over 15 min. Aspiration of approximately 75 % of the total hematoma was performed 6 h after induction of severe ICH. The effects of hematoma aspiration on hematoma volume, mortality, oxidative stress, ATP levels, mitochondrial dysfunction, and neurological function were measured in rats.</div></div><div><h3>Results</h3><div>Severe ICH induction increased hematoma volume, neurological deficits, and mortality. Hematoma aspiration abolished mortality and significantly reduced hematoma volume, and neurological deficits. In addition, hematoma aspiration ameliorated the pronounced mitochondrial dysfunction responsible for the failure of energy production and excessive oxidative stress associated with severe hemorrhagic injury. Hematoma aspiration also modulated mitochondrial biogenesis and mitophagy, thereby promoting mitochondrial homeostasis. Markers of neuroinflammation, including iNOS, MMP9, and MPO, were elevated in severe ICH but attenuated by hematoma aspiration.</div></div><div><h3>Conclusion</h3><div>This study established an animal model of severe ICH and provides valuable insights into the complex pathogenesis of severe ICH. The results showed that hematoma aspiration effectively ameliorates mitochondrial dysfunction, oxidative stress, and neuroinflammation, highlighting its potential as a therapeutic intervention.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"385 ","pages":"Article 115098"},"PeriodicalIF":4.6,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799587","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":"Data reporting quality and semantic interoperability increase with community-based data elements (CoDEs). Analysis of the open data commons for spinal cord injury (ODC-SCI)","authors":"Anushka Sheoran ,&nbsp;Kenneth A. Fond ,&nbsp;Lex Maliga Davis ,&nbsp;J. Russell Huie ,&nbsp;Romana Vavrek ,&nbsp;P.J. Axtman ,&nbsp;Vance Lemmon ,&nbsp;John L. Bixby ,&nbsp;Ubbo Visser ,&nbsp;John C. Gensel ,&nbsp;Karim Fouad ,&nbsp;Adam R. Ferguson ,&nbsp;Jeffrey S. Grethe ,&nbsp;Anita Bandrowski ,&nbsp;Maryann E. Martone ,&nbsp;Abel Torres-Espin","doi":"10.1016/j.expneurol.2024.115100","DOIUrl":"10.1016/j.expneurol.2024.115100","url":null,"abstract":"<div><div>Data interoperability is crucial for effectively combining data for scientific inquiry. To facilitate interoperability, data standards such as a common definition of variables are often developed. The Open Data Commons for Spinal Cord Injury (<span><span>odc-sci.org</span><svg><path></path></svg></span>) has established an initial set of community-based data elements (CoDEs)—a minimal set of variables for sharing—to promote data interoperability in SCI research, aligning with FAIR (Findable, Accessible, Interoperable, and Reusable) data principles. We sought to understand the use of CoDEs by the SCI community to inform current standards adherence and future standards development. We systematically analyzed 39 public datasets in relation to 17 required CoDEs and found variations between reported data and the structure specified by the CoDEs. Overall, we found that the enforcement of data standards improved reporting rates of CoDEs variables. Notably, different variables were found to require different levels of curation to ensure semantic equivalence among datasets. We also uncovered specific reporting habits of researchers such as formatting and naming patterns. A need for different data standards based on the nature of the study (e.g., human study, derivative study) was realized alongside a detailed list of issues that should be addressed when implementing such standards. Among the various approaches to developing data standards, ODC-SCI adopted a semi-formal approach by creating standards that are easy to adopt by the user. Our data-driven evaluation of actual reporting behavior shows that this flexibility can lead to subsequent problems in harmonization. This study serves as a baseline analysis of reporting behaviors for shaping and facilitating data standards.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"385 ","pages":"Article 115100"},"PeriodicalIF":4.6,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794408","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":"VX-765 attenuates secondary damage and β-amyloid accumulation in ipsilateral thalamus after experimental stroke in rats","authors":"Yu-Bin Liang ,&nbsp;Ri-Xin Luo ,&nbsp;Zhen Lu ,&nbsp;Ying Mao ,&nbsp;Ping-Ping Song ,&nbsp;Qiao-Wei Li ,&nbsp;Zhi-Qiang Peng ,&nbsp;Yu-Sheng Zhang","doi":"10.1016/j.expneurol.2024.115097","DOIUrl":"10.1016/j.expneurol.2024.115097","url":null,"abstract":"<div><div>Focal cortical infarction can result both in the accumulation of Aβ in as well as further secondary damage and inflammation within the ipsilateral thalamus. VX-765 is a potent and selective small-molecule capable of inhibiting caspase-1, which has been shown to exhibit active neuroprotection properties in multiple disease. However, the neuroprotection efficacy of VX-765 as a means of attenuating secondary damage after MCAO remains uncertain. As such, we sought to determine the ability of VX-765 to alter thalamic Aβ accumulation, secondary damage, and sensory deficits in rats of focal cortical infarction. A rat model of distal branch of middle cerebral artery occlusion (dMCAO) was used to evaluate the effects of the VX-765 on the secondary damage and β-amyloid accumulation in ipsilateral thalamus after dMCAO in rats. The activation of astrocyte and microglia, loss of neuron, and damage to sensory function were detected weekly till 4 weeks after modeling. VX-765 was injected intraperitoneally delayed after 7 days injury and the status of secondary damage, inflammation and β-amyloid accumulation in ipsilateral thalamus after dMCAO were examined.Our results revealed that VX-765 markedly reduce sensory deficits in these rats, suppressing secondary damage through reductions in APP and accumulations of Aβ with an accompanying reduction in both neuronal loss, astrocyte and microglia activation. VX-765 markedly inhibited NLRP3 and caspase-1, and downregulation of ASC, GSDMD, IL-1β, and IL-18 in the ipsilateral thalamus after MCAO. Our results further suggested that VX-765 may regulate secondary damage via control inflammation and suppressing the production of pro-inflammatory factors such as iNOS, TNF-α, IL-6 and COX2 that are produced downstream NF-κB signaling. Taken together, VX-765 is well-suited to attenuate secondary damage and accumulations of Aβ, improving recovery from sensory deficits and cognitive deficits after MCAO, at least in part via suppressing pyroptosis and inflammation.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"385 ","pages":"Article 115097"},"PeriodicalIF":4.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794436","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":"Inhibition of histamine receptor 3 alleviates sevoflurane-induced hypomyelination and neurobehavioral deficits","authors":"Ji Che ,&nbsp;Yuanyuan Wu ,&nbsp;Jing Dong ,&nbsp;Xuliang Jiang ,&nbsp;Li Yang ,&nbsp;Yali Chen ,&nbsp;Jun Zhang","doi":"10.1016/j.expneurol.2024.115086","DOIUrl":"10.1016/j.expneurol.2024.115086","url":null,"abstract":"<div><h3>Background</h3><div>Inhalational anesthetic sevoflurane can cause myelination damage in developing brain. This study examines the effects of histamine receptor 3 (H3) antagonist thioperamide on sevoflurane-induced hypomyelination and neurobehavioral deficits.</div></div><div><h3>Methods</h3><div>Neonatal C57BL/6 mice were exposed to sevoflurane for consecutive three days and treated with H3 receptor antagonist thioperamide. Myelination was assessed in the hippocampus and corpus callosum. The neurobehavioral functions were also examined. Primary oligodendrocyte progenitor cells (OPCs) were used for in vitro experiments and the underlying mechanism.</div></div><div><h3>Results</h3><div>Inhibition of H3 receptor with thioperamide significantly alleviated sevoflurane-induced impairments in myelination and neurobehavioral functions. In vitro experiments showed that thioperamide reversed the effects of sevoflurane on OPCs migration, proliferation and differentiation into mature oligodendrocytes. Mechanistically, thioperamide improved sevoflurane-induced hypomyelination may through H3 receptor-mediated GSK-3β/β-catenin pathway.</div></div><div><h3>Conclusion</h3><div>H3 receptor antogonist thioperamide could protect developing brain against hypomyelination and neurobehavioral deficits after repeated sevoflurane exposure. Therefore H3 receptor is a potential target for preventing anesthetic-induced developmental neurotoxicity.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"385 ","pages":"Article 115086"},"PeriodicalIF":4.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785021","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":"Transcutaneous auricular vagus nerve stimulation attenuates stroke-heart syndrome: The role of parasympathetic activity","authors":"Weina Wang ,&nbsp;Mengmei Wang ,&nbsp;Can Ma ,&nbsp;Yu Zhang ,&nbsp;Xuefei Li ,&nbsp;Yuting Wei ,&nbsp;Xin Fu ,&nbsp;Lijuan Zhang ,&nbsp;Tianhua Liu ,&nbsp;Wenzhi Li","doi":"10.1016/j.expneurol.2024.115094","DOIUrl":"10.1016/j.expneurol.2024.115094","url":null,"abstract":"<div><div>Stroke induces cardiac dysfunction, which increases poststroke mortality and morbidity. An imbalance in the autonomic nervous system resulting from brain injury may serve as the underlying mechanism. The present study investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) attenuates poststroke cardiac dysfunction by activating the parasympathetic nervous system. Adult male mice were subjected to transient middle cerebral artery occlusion (MCAO) and reperfusion surgery. The mice in the treatment group received repeated taVNS starting 60 min after the onset of cerebral ischemia. To assess whether the effects of taVNS were associated with parasympathetic activity, the MCAO mice in the atropine group received intraperitoneal injections of atropine to inhibit parasympathetic activity prior to taVNS. taVNS significantly increased the left ventricular ejection fraction (EF), attenuated myocardial apoptosis, reduced myocardial hypertrophy, and reduced fibrosis following stroke. The beneficial effects of taVNS on cardiac dysfunction were abolished by atropine administration. Heart rate variability (HRV) analysis and western blot analysis revealed that taVNS increased parasympathetic activity but decreased sympathetic dominance in mice with MCAO. Furthermore, the cardioprotective effects of taVNS were associated with muscarinic acetylcholine receptor activation, PI3K–Akt pathway modulation, and eNOS regulation in the heart. Therefore, taVNS alleviates cardiac dysfunction after stroke and is associated with activation of the parasympathetic nervous system.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"385 ","pages":"Article 115094"},"PeriodicalIF":4.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785023","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":"Exercise your graft – An important lesson for cell replacement therapy for Parkinson's disease","authors":"Marcel M. Daadi ,&nbsp;Evan Y. Snyder","doi":"10.1016/j.expneurol.2024.115085","DOIUrl":"10.1016/j.expneurol.2024.115085","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a complex multisystem, chronic and so far, incurable disease affecting millions of people worldwide. With the continuing need for better therapeutic options for PD, there is a global renewed interest in cell replacement therapy due to progress in using pluripotent stem cells as an unlimited source of dopaminergic (DA) neurons for cell transplantation. Despite the significant progress made, obstacles remain that interfere with the restoration of functional circuits by DA grafts. The functional connectivity between DA grafts and host cells may be enhanced by adjunctive therapies, such as physical activity. Exercise modalities, such as use of treadmill, enhance neuroplasticity and improve motor and cognitive functions in PD patients. The patients are able to re-learn movement and adjust their posture, which, in turn, results in short term-reduced rigidity and improved stride length and cadence. By stabilizing selected active inputs and eliminating inactive ones, activity-dependent mechanisms fine-tune new neural circuits for optimal connection and physiological function. This communication will review the mechanisms and synergies between cell replacement therapy and physical and cognitive training to enhance induced pluripotent stem cell-mediated functional reinnervation of the striatum in PD.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"385 ","pages":"Article 115085"},"PeriodicalIF":4.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778952","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":"Acteoside alleviates salsolinol-induced Parkinson's disease by inhibiting ferroptosis via activating Nrf2/SLC7A11/GPX4 pathway","authors":"Hongquan Wang ,&nbsp;Shuang Wu ,&nbsp;Xiaodong Jiang ,&nbsp;Wenjing Li ,&nbsp;Qiang Li ,&nbsp;Huiyan Sun ,&nbsp;Yumin Wang","doi":"10.1016/j.expneurol.2024.115084","DOIUrl":"10.1016/j.expneurol.2024.115084","url":null,"abstract":"<div><div>Salsolinol (SAL), i.e.1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroiso-quinoline, is a dopamine metabolite and endogenous neurotoxin that is toxic to dopaminergic neurons, and is involved in the genesis of Parkinson's disease (PD). However, the machinery underlying SAL induces neurotoxicity in PD are still being elucidated. In the present study, we first used RNA sequencing (RNAseq) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to detect differentially expressed genes in SAL-treated SH-SY5Y cells. We found that ferroptosis-related pathway was enriched by SAL, which was validated by in vitro and in vivo SAL models. SAL inducing ferroptosis through downregulating SLC7A11/GPX4 in SH-SY5Y cells, which neurotoxic effect was reversed by ferroptosis inhibitors deferoxamine (DFO) and ferrostatin-1 (Fer-1). Acteoside, a phenylethanoid glycoside of plant origin with neuroprotective effect, attenuates SAL-induced neurotoxicity by inhibiting ferroptosis in in vitro and in vivo PD models through upregulating SLC7A11/GPX4. Mechanistically, acteoside activates Nrf2. Nrf2 inhibitor ML385 abolished acteoside-mediated increased SLC7A11/GPX4 and neuroprotection against SAL in SH-SY5Y cells. Meanwhile, the PI3K inhibitor LY294002 suppressed the acteoside-induced Nrf2 expression and ensued decreased expression of SLC7A11/GPX4 in SAL-treated SH-SY5Y cells. Taken together, these results demonstrate that salsolinol-induced PD through inducing ferroptosis via downregulating SLC7A11/GPX4. Acteoside attenuates SAL-induced PD through inhibiting ferroptosis via activating PI3K/Akt-dependant Nrf2. The present study revealed a novel molecular mechanisms underlining SAL-induced neurotoxicity via induction of ferroptosis in PD, and uncovered a new pharmacological effect against PD through inhibiting ferroptosis. This study highlights SAL-induced ferroptosis -dependent neurotoxicity as a potential therapeutic target in PD.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"385 ","pages":"Article 115084"},"PeriodicalIF":4.6,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779732","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":"Editorial: Intersection of neural activity, synuclein and Parkinson's disease","authors":"Ken Nakamura","doi":"10.1016/j.expneurol.2024.115091","DOIUrl":"10.1016/j.expneurol.2024.115091","url":null,"abstract":"","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"385 ","pages":"Article 115091"},"PeriodicalIF":4.6,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791329","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":"Delayed changes in the transcriptomic profile of cerebral arteries in a rat model of subarachnoid hemorrhage","authors":"Gonzalo Revilla-González ,&nbsp;María del Carmen González-Montelongo ,&nbsp;Elton J.R. Vasconcelos ,&nbsp;Juan Ureña ,&nbsp;Jian Shi ,&nbsp;Antonio Castellano","doi":"10.1016/j.expneurol.2024.115074","DOIUrl":"10.1016/j.expneurol.2024.115074","url":null,"abstract":"<div><div>Aneurismal subarachnoid hemorrhage (aSAH) is a neurovascular disease characterized by blood released into the subarachnoid space due to rupture of the cerebral arteries. After the onset of bleeding, secondary associated vasospasm (VSP) remains a dramatic side effect that causes severe comorbidities. We analyzed alterations in the expression profiles of arteries from a rat model of SAH using microarray and bioinformatics approaches. A single injection autologous blood rat model, previously characterized in our laboratory, was used. We performed a total RNA extraction and a microarray analysis of cerebral arteries from animals 7 days after surgery to study the delayed transcriptional changes induced by SAH. To assess the functional relationship between differently expressed genes, we run a combination of gene enrichment tools: GSEA, ClueGO, and ClusterProfiler. Our results showed that in SAH animals, the gene sets related to inflammation and immune system activation were up-regulated; genes related to the pathways involved in the regulation of muscle contraction had their expression disturbed; and the gene categories associated with DNA damage and repair were overrepresented. In conclusion, our results suggest that, after the SAH insult, multiple mechanisms, rather than a single cause, are activated at the same time in the cerebral vessels to trigger vascular alterations.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115074"},"PeriodicalIF":4.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750502","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}