Brain Research最新文献

{"title":"H2S improves hippocampal synaptic plasticity in SPS rats via PI3K/AKT signaling pathway","authors":"Shuwen Yu ,&nbsp;Wei Zhang ,&nbsp;Xixi Wang ,&nbsp;Qian Luo ,&nbsp;Bing Gu ,&nbsp;Yijing Zhao ,&nbsp;Dexiang Liu ,&nbsp;Zhen Wang","doi":"10.1016/j.brainres.2024.149286","DOIUrl":"10.1016/j.brainres.2024.149286","url":null,"abstract":"<div><div>Post-traumatic stress disorder (PTSD) is a severe mental illness that could impose heavy burdens on individuals and society, but effective and precise treatment modalities are unknown. The level of hydrogen sulfide (H₂S) in the brain plays an important role in psychiatric diseases. However, it is still unclear whether PTSD exposure could affect the level of H₂S and whether there is a correlation between H₂S levels and the pathogenesis of PTSD. In this study, we selected single prolonged stress (SPS) as a PTSD model and found that SPS exposure decreased the endogenous H₂S content accompanied by abnormal behavioral changes and dysregulation of the hippocampal synaptic plasticity in SPS rats. We further found that the exogenous administration of H₂S could alleviate PTSD-like behaviors and improve hippocampal synaptic plasticity in SPS rats. In addition, we further used the phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 to interfere with the PI3K/AKT/BDNF signaling pathway. It was found that LY294002 significantly blocked the anti-anxiety effect and the improvement in synaptic plasticity derived from the exogenous administration of H₂S in SPS rats. These results suggested that the endogenous H₂S content was decreased in SPS rats, and that the exogenous administration of H₂S could ameliorate abnormal disorders and improve hippocampal synaptic plasticity by mediating the PI3K/AKT pathway.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1845 ","pages":"Article 149286"},"PeriodicalIF":2.7,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457870","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}

{"title":"Early divergent modulation of NLRP2′s and NLRP3′s inflammasome sensors vs. AIM2′s one by signals from Aβ·Calcium-sensing receptor complexes in human astrocytes","authors":"Anna Chiarini ,&nbsp;Ubaldo Armato ,&nbsp;Li Gui ,&nbsp;Meifang Yin ,&nbsp;Shusen Chang ,&nbsp;Ilaria Dal Prà","doi":"10.1016/j.brainres.2024.149283","DOIUrl":"10.1016/j.brainres.2024.149283","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Alzheimer’s disease (AD), the most prevalent human dementia, is driven by accruals of extracellular Aβ&lt;sub&gt;42&lt;/sub&gt; senile patches and intracellular neurofibrillary tangles of hyperphosphorylated Tau (p-Tau) proteins. AD’s concurrent neuroinflammation is prompted by innate immunity-related cytosolic protein oligomers named inflammasomes. Upon proper “first” (priming) and “second” (activating) signals, inflammasomes overproduce proinflammatory Interleukin (IL)-1β, and IL-18 while cleaving pyroptosis-promoting Gasdermin D’s N-terminal fragments. Our earlier studies highlighted that in pure monocultures, exogenous Aβ&lt;sub&gt;25-35&lt;/sub&gt;-treated nonproliferating human cortical astrocytes (HCAs) made and released surpluses of endogenous Aβ&lt;sub&gt;42&lt;/sub&gt;-oligomers (−os) and p-Tau-os, just as alike-treated human cortical neurons did. Aβ&lt;sub&gt;25-35&lt;/sub&gt;-exposed HCAs also over-released NO, VEGFA, and IL-6. Aβ•CaSR (Aβ·Calcium-Sensing Receptor) complexes generated intracellular signals mediating all such neurotoxic effects since CaSR’s negative allosteric modulators (aka NAMs or calcilytics, e.g., NPS2143) fully suppressed them. However, it had hitherto remained unexplored whether signals from Aβ·CaSR complexes also induced the early expression and/or activation of NOD-like 2 (NLRP2) and 3 (NLRP3) and of PYHIN absent in melanoma 2 (AIM2) inflammasomes in monocultured HCAs. To clarify this topic, we used &lt;em&gt;in-situ&lt;/em&gt;-Proximity Ligation, qRT-PCR, double antibody arrays, immunoblots, and Caspase 1/4 enzymatic assays. Aβ·CaSR complexes quickly assembled on HCAs surface and issued intracellular signals activating Akt and JAK/STAT axes. In turn, the latter upregulated NLRP2 and NLRP3 PRRs (pattern recognition receptors) yet downregulated AIM2. These effects were specific, being significantly hindered by NPS2143 and inhibitors of PI3K (LY294002), AMPKα (Dorsomorphin), mTOR (Torin1), and JAK/TYK (Brepoticinib). A wide-spectrum inhibitor, Bay11-7082, intensified the Aβ·CaSR/Akt/JAK/STAT axis-driven opposite control of NLRP3’s and AIM2’s PRR proteins without affecting NLRP2 PRR upregulation. However, the said effects on the PRRs proteins vanished within 24-h. Moreover, Aβ·CaSR signals neither concurrently changed ASC, pro-IL-1β, and Gasdermin-D (holo- and fragments) protein levels and Caspases 1 and 4 enzymatic activities nor induced pyroptosis. Therefore, Aβ·CaSR cues acted as “first (priming) signals” temporarily increasing NLRP2 and NLRP3 PRRs expression without activating the corresponding inflammasomes. The neatly divergent modulation of NLRP3’s &lt;em&gt;vs&lt;/em&gt;. AIM2’s PRR proteins by Aβ·CaSR cues and by Bay11-7082 suggests that, when bacterial or viral DNA fragments are absent, AIM2 might play “anti-inflammasomal” or other roles in HCAs. However, Bay11-7082’s no effect on NLRP2 PRR overexpression also reveals that CaSR’s downstream mechanisms controlling inflammasomes’ sensors are quite complex in HCAs, and hence, given AD’s impact on human health, well w","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149283"},"PeriodicalIF":2.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in plasma lipid profiles, but not in glucose metabolism in patients with first-episode antipsychotics-naïve schizophrenia","authors":"Shen Li ,&nbsp;Nannan Liu ,&nbsp;Dan Qi ,&nbsp;Lichao Niu ,&nbsp;Yanzhe Li ,&nbsp;Chenghao Lu ,&nbsp;Yeqing Dong ,&nbsp;Xinxu Wang ,&nbsp;Jie Li ,&nbsp;Xiangyang Zhang","doi":"10.1016/j.brainres.2024.149282","DOIUrl":"10.1016/j.brainres.2024.149282","url":null,"abstract":"<div><h3>Background</h3><div>First-episode antipsychotics-naïve schizophrenia (FEAN-SCZ) is associated with abnormalities in glucose and lipid metabolism. While sex differences in the incidence and severity of SCZ and metabolic abnormalities have been documented, the specific metabolic abnormalities between the sexes remain unclear. The study aimed to investigate sex-specific differences in plasma glycolipid profiles in FEAN-SCZ patients.</div></div><div><h3>Methods</h3><div>A total of 172 FEAN-SCZ patients (male/female: 83/89) and 31 healthy controls (male/female: 14/17) were recruited. Psychopathology assessment was conducted using the Positive and Negative Syndrome Scale (PANSS). Glycolipid profiles, including oral glucose tolerance test (OGTT), fasting glucose, insulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were examined in all participants.</div></div><div><h3>Results</h3><div>FEAN patients displayed significantly higher fasting and 2-hour glucose levels compared to healthy controls (both <em>p</em> &lt; 0.001). Impaired glucose tolerance (IGT) prevalence in male patients was 24.1 % (n = 20) and 25.9 % (n = 23) in females, contrasting with 0 % (n = 0) in the control group. FEAN patients exhibited elevated blood insulin and TC levels (both <em>p</em> &lt; 0.05) and increased insulin resistance measured by HOMA-IR (<em>p</em> &lt; 0.01). Among male patients, those with IGT had significantly higher TC, TG and LDL levels than non-IGT patients (all <em>p</em> &lt; 0.05), while no significant differences were observed in female patients between IGT and non-IGT groups. Body mass index (BMI), TG and HDL levels were identified as significant predictors of IGT in male FEAN patients.</div></div><div><h3>Conclusions</h3><div>IGT is present in a subset of FEAN-SCZ patients. Male patients with IGT exhibit distinct alterations in plasma lipid profiles compared to non-IGT patients.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149282"},"PeriodicalIF":2.7,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457871","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}

{"title":"Electrophysiological measures of patients with unilateral spatial neglect after brain disease: A systematic review","authors":"Zihan Yao,&nbsp;Guixiang Shan,&nbsp;Weiqun Song,&nbsp;Linlin Ye","doi":"10.1016/j.brainres.2024.149260","DOIUrl":"10.1016/j.brainres.2024.149260","url":null,"abstract":"<div><h3>Introduction</h3><div>The investigation of brainwave changes during the recovery process of unilateral spatial neglect (USN) has garnered considerable attention in recent years. This paper presents an updated overview of the evolving brainwave patterns during USN rehabilitation, aiming to predict clinical outcomes and guide the selection of effective recovery strategies.</div></div><div><h3>Methods</h3><div>A systematic review was conducted, encompassing English literature published up to June 2024. Databases including PubMed, Web of Science, and clinical trials were utilized. The included studies assessed brainwaves using electroencephalography (EEG) in at least one group with USN. However, the diverse nature of these studies posed challenges for a quantitative synthesis.</div></div><div><h3>Results</h3><div>The final quantitative synthesis comprised 36 studies, incorporating a total of 4517 data points. The analysis revealed abnormalities in alpha, beta, and gamma brainwave activity, along with alterations in the functional monitoring of the alpha band during USN rehabilitation. Additionally, reductions were observed in specific brainwave components such as P1, N1, P2, P300, early directing attention negativity (EDAN), late directing attention positivity (LDAP), and contingent negative variation (CNV). However, findings regarding measures of synchrony, connectivity, and evoked responses across different frequency bands exhibited variability.</div></div><div><h3>Conclusions</h3><div>Various indicators of brainwave activity displayed changes at different stages of post-stroke neglect rehabilitation, highlighting the significance of neural network dysfunction in this process. Nonetheless, due to the diversity of the studies, further investigation is necessary to achieve a more comprehensive understanding in future research endeavors.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1845 ","pages":"Article 149260"},"PeriodicalIF":2.7,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ameliorative effects of Akkermansia muciniphila on anxiety-like behavior and cognitive deficits in a rat model of Alzheimer’s disease","authors":"Hamideh Maftoon ,&nbsp;Seyed Davar Siadat ,&nbsp;Samira Tarashi ,&nbsp;Erfan Soroush ,&nbsp;Mohammad Basir Asefi ,&nbsp;Abbas Rahimi Foroushani ,&nbsp;Mohammad Mehdi Soltan Dallal","doi":"10.1016/j.brainres.2024.149280","DOIUrl":"10.1016/j.brainres.2024.149280","url":null,"abstract":"<div><div>Alzheimer’s Disease (AD) is the primary neurodegenerative disorder in the elderly, lacking a definitive treatment. The gut microbiota influences the gut-brain axis by aiding in hypothalamic–pituitary–adrenal (HPA) axis development and neuromodulator production. Research links AD and gut microbiota, suggesting gut microbiota regulation could be a therapeutic approach for AD. This study explores <em>Akkermansia muciniphila</em>’s impact on preventing AD. This research investigates the effect of <em>A. muciniphila</em> consumption (1 × 10⁹ CFU) on tau protein-induced AD rats compared to a control group. Rats were divided into four groups: sham, sham + Akk, AD (tau-induced rats), and AD + Akk (tau-induced rats treated with <em>A. muciniphila</em>). <em>A. muciniphila</em> gavage lasted five weeks. Rats underwent qRT-PCR analysis to assess mRNA expression of pro-inflammatory factors (<em>TNF-α</em>, <em>IL-6</em>, <em>IL-1β</em>, <em>IFN-γ</em>) in the hippocampus. Behavioral tests included Morris Water Maze (MWM), Passive Avoidance Memory Test (Shuttle box), Elevated Plus Maze (EPM), and marble burying. After five weeks of <em>A. muciniphila</em> treatment, anxiety-like behavior significantly decreased. The AD group receiving <em>A. muciniphila</em> showed improved spatial and recognition memory compared to the AD group. Pro-inflammatory cytokine levels (<em>TNF-α</em>, <em>IL-1β</em>, <em>IL-6</em>, <em>IFN-γ</em>) decreased. <em>A. muciniphila</em> effectively reduces cognitive impairments and anxiety-related behavior, showing promise as an AD therapeutic by influencing the gut-brain axis.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1845 ","pages":"Article 149280"},"PeriodicalIF":2.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457866","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}

{"title":"Delayed-and-abbreviated environmental enrichment after traumatic brain injury confers neurobehavioral benefits similar to immediate-and-continuous exposure","authors":"Rachel A. Bittner ,&nbsp;Anna M. Greene ,&nbsp;Jacob B. Leary ,&nbsp;Hailey M. Donald ,&nbsp;Haley E. Capeci ,&nbsp;Eleni H. Moschonas ,&nbsp;Jeffrey P. Cheng ,&nbsp;Corina O. Bondi ,&nbsp;Anthony E. Kline","doi":"10.1016/j.brainres.2024.149281","DOIUrl":"10.1016/j.brainres.2024.149281","url":null,"abstract":"<div><div>Environmental enrichment (EE) consists of increased living space, complex stimuli, and social interaction that collectively confer neurobehavioral benefits in preclinical models of traumatic brain injury (TBI). The typical EE approach entails implementation immediately after surgery and continual exposure, which is not clinically applicable, as TBI patients often only receive rehabilitation after critical care, and then only for a few hours per day. We are focused on developing a clinically relevant model of neurorehabilitation by refining the timing of initiation and duration of EE exposure after TBI. The goal of this experiment is to compare the typical EE approach to paradigms where EE is delayed by 3 or 7 days after TBI and then provided for only 6 h per day, which better mimics the clinic. The hypothesis is that the delayed-and-abbreviated EE paradigms will promote neurobehavioral benefits like the typical approach of immediate-and-continuous exposure. To test the hypothesis, anesthetized adult male rats underwent a controlled cortical impact of moderate severity (2.8 mm deformation at 4 m/s) or sham injury and then were randomly assigned to post-operative EE or standard (STD) housing. Motor ability, spatial learning, and memory retention were assessed. The hypothesis was confirmed as all EE-treated groups performed better than the STD group in all behavioral assessments (<em>p</em> &lt; 0.05) and did not differ from one another (<em>p</em> &gt; 0.05). The ability of EE to provide significant behavioral benefits even when delayed and delivered in moderation affords further support for EE as a preclinical model of neurorehabilitation and offers greater insight into the length of the therapeutic window.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149281"},"PeriodicalIF":2.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2-BFI protects against ischemic stroke by selectively acting on NR2B-containing NMDA receptors","authors":"Shasha Xu ,&nbsp;Jiaou Chen ,&nbsp;Chunfei Xu ,&nbsp;Ye Xu ,&nbsp;Lu Xu ,&nbsp;Meiqi Zhao ,&nbsp;Tong Xu ,&nbsp;Yungang Cao ,&nbsp;Peijun Li ,&nbsp;Zhao Han","doi":"10.1016/j.brainres.2024.149284","DOIUrl":"10.1016/j.brainres.2024.149284","url":null,"abstract":"<div><h3>Background and purpose</h3><div>The intricate roles of NMDA receptors, specifically those containing the NR2A or NR2B subunit, in ischemic stroke pathology necessitate targeted therapeutic investigations. Building on our prior discovery showcasing the neuroprotective potential of 2-(benzofuran-2-yl)-2-imidazoline (2-BFI), an imidazoline I2 receptor ligand, in inhibiting NMDA receptor currents during ischemic stroke, this study aims to elucidate the specific impact of 2-BFI on NR2A- and NR2B-containing NMDARs.</div></div><div><h3>Experimental approach</h3><div>Through whole-cell patch-clamp techniques, we observed an inhibition by 2-BFI on NR2A-containing NMDAR currents (IC50 = 238.6 μM) and NR2B-containing NMDAR currents (IC50 = 18.47 μM). Experiments with HEK293 cells expressing exogenous receptor subunits revealed a significantly higher affinity of 2-BFI towards NR2B-containing NMDARs. In vivo studies involved the co-administration of 2-BFI and the NR2A subunit antagonist NVP-AAM077 in rats subjected to transient middle cerebral artery occlusion (tMCAO).</div><div>Key results</div><div>2-BFI exhibited a pronounced preference for inhibiting NR2B-containing NMDAR currents, leading to a notable mitigation of cerebral ischemic injury when administered in conjunction with NVP-AAM077 in the tMCAO rat model. Furthermore, alterations in the expression of downstream proteins specific to NR2B-containing NMDA receptors were observed, suggesting targeted molecular effects.</div><div>Conclusion and implications</div><div>This study unveils the neuroprotective potential of 2-BFI in ischemic stroke by selectively inhibiting NR2B-containing NMDA receptors. These findings lay the foundation for precise therapeutic strategies, showcasing the differential roles of NR2A and NR2B subunits and paving the way for advancements in targeted interventions for ischemic stroke treatment.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1845 ","pages":"Article 149284"},"PeriodicalIF":2.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457865","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}

{"title":"DHA plays a protective role in cerebral ischemia–reperfusion injury by affecting macrophage/microglia type polarization","authors":"Jin Yimin ,&nbsp;Pu Tiantian ,&nbsp;Zhang Tongshuai ,&nbsp;Sun Qixu ,&nbsp;Han Yang ,&nbsp;Han Siyu ,&nbsp;Wang Guangyou ,&nbsp;Yang Shanshan ,&nbsp;Zhang Yao","doi":"10.1016/j.brainres.2024.149278","DOIUrl":"10.1016/j.brainres.2024.149278","url":null,"abstract":"<div><div>A close correlation exists between the macrophage/microglia(MΦ/MG) polarization states and the development of cerebral ischemia and reperfusion (I/R). Therefore it is of great significance to research on how to modulate the MΦ/MG states for improved patient outcomes. In particular, regulatory mechanisms involved in this process remain to be identified. Hereby, we aim to shed light on how docosahexaenoic acid (DHA) actively modulates the switch between M1 and M2 macrophage states by restraining the NACHT-LRR-PYD-containing protein three inflammasome (NALP3). We found that NALP3-positive cells were detected in clinical human cerebral infarction tissue samples and the mouse tMCAO model. In mice after DHA treatment, the number of NALP3-positive cells was significantly reduced, significantly decreasing infarct volume and improving the postoperative physical status of mice. NALP3-positive cells were found to be MΦ/MG after co-staining with CD11b. By extracting peritoneal macrophages, it was verified that DHA inhibited the activation of NALP3 and regulated the transformation of M1 and M2 cells, thereby reducing I/R injury.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149278"},"PeriodicalIF":2.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457868","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}

{"title":"Two-phase therapy for improving neuroprotection and neurogenesis: Preventive use of omega fatty acids plus Copolymer-1 immunization after stroke","authors":"Yolanda Cruz-Martínez ,&nbsp;Karla Cantú ,&nbsp;Gerardo Ojeda ,&nbsp;Vanessa Gálvez-Susano ,&nbsp;Stella Arias-Santiago ,&nbsp;Andrea P. Ibarra-García ,&nbsp;Cesar V. Borlongan ,&nbsp;Humberto Carrasco-Vargas ,&nbsp;Marco Antonio Vargas-Hernández ,&nbsp;Antonio Ibarra","doi":"10.1016/j.brainres.2024.149277","DOIUrl":"10.1016/j.brainres.2024.149277","url":null,"abstract":"<div><div>Stroke is a major global health issue, ranking as the second leading cause of death and the primary cause of disability worldwide. However, current therapeutic options remain limited. Nutritional supplementation as a form of primary prevention stands as a potential stroke therapeutic. In particular, the intake of omega-3 fatty acids (omega-3FA) exerts anti-inflammatory and neuroprotective effects that help reduce the risk of stroke. In parallel, treatment with Copolymer-1 (COP-1), a peptide with immunomodulatory properties through Th1/Th2/Th3 phenotype switching, similarly affords neuroprotective and neurorestorative effects in stroke models. To investigate the combined effects of these treatments, we designed a two-phase therapy: the first phase involved preventive supplementation with omega-3FA, while the second phase included COP-1 immunization following stroke injury. Sprague-Dawley rats were randomly assigned to one of the four groups: 1) control, 2) omega-3FA, 3) COP-1, and 4) omega-3FA + COP-1. Omega-3FAs were administered for 28 days before inducing stroke. Thirty minutes after reperfusion, the respective groups were immunized with COP-1. Seven days post-stroke, neurological deficits were assessed using the Zea-Longa scale, infarct volumes with 2,3,5-triphenyltetrazolium chloride (TTC) staining, and levels of neurogenesis via immunofluorescence imaging. The results showed that the two-phase therapy produced significant synergistic effects, markedly reducing neurological deficits, and infarct volumes, while enhancing neurogenic activities in neurogenic niches. This combined approach underscores the potential of integrating nutritional and pharmacological strategies to enhance stroke recovery.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149277"},"PeriodicalIF":2.7,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457872","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}

{"title":"Therapeutic effects of exercise on depression: The role of microglia","authors":"Li Li ,&nbsp;Li Ren ,&nbsp;Bing Li ,&nbsp;Chaomeng Liu","doi":"10.1016/j.brainres.2024.149279","DOIUrl":"10.1016/j.brainres.2024.149279","url":null,"abstract":"<div><div>Major depressive disorder<!--> <!-->adversely affects mental health. Traditional therapeutic approaches, including medication, psychological intervention, and physical therapy, exert beneficial effects on depression. However, these approaches are associated with some limitations, such as high cost, adverse reactions, recurrent episodes, and low patient adherence. Previous studies have demonstrated that exercise therapy can effectively mitigate depressive symptoms, although the underlying mechanism has not been elucidated. Recent studies have suggested that depression is a microglial disease. Microglia regulate the inflammatory response, synaptic plasticity, neurogenesis, kynurenine pathway and the activation of hypothalamic-pituitary-adrenal axis, all of which affect depression. Exercise therapy is reported to shift the balance of microglial M1/M2 polarization in the hippocampus, frontal lobe, and striatum, suppressing the release of pro-inflammatory factors and consequently alleviating behavioral deficits in animal models of depression. Further studies are needed to examine the specific effects of different exercise regimens on microglia to identify the exercise regimen with the best therapeutic effect.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149279"},"PeriodicalIF":2.7,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457895","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}