Journal of integrative neuroscience最新文献

{"title":"Sodium Rutin Alleviates Neuronal Apoptosis and Promotes Locomotor Recovery in Distractive Spinal Cord Injury via ErbB4 and ROS Signaling.","authors":"Weishi Liang, Yeqiu Xu, Junrui Jonathan Hai, Duan Sun, Yihan Yang, Chen Wang, Peng Yin, Yajin Liao, Bo Han, Xianjun Qu, Yong Hai","doi":"10.31083/JIN51000","DOIUrl":"https://doi.org/10.31083/JIN51000","url":null,"abstract":"<p><strong>Background: </strong>Distractive spinal cord injury (DSCI), a severe complication of spinal deformity correction surgery, is characterized by rapid neuronal loss. However, the molecular mechanisms linking mechanical distraction to apoptosis remain unclear. Here, we tested whether sodium rutin (NaR), a water-soluble rutin derivative with improved oral bioavailability, mitigates DSCI.</p><p><strong>Methods: </strong>We employed an <i>in vivo</i> rat DSCI model and an <i>in vitro</i> mechanical distraction (DIS) model using neuronal cells. The therapeutic efficacy of NaR was evaluated using locomotor function assessments (Basso-Beattie-Bresnahan score and footprint analysis), histopathology, and transmission electron microscopy. Molecular docking simulations were performed to predict the binding affinity of NaR to Erb-B2 receptor tyrosine kinase 4 (ErbB4). Mechanistic investigations targeting the ErbB4/protein kinase B (Akt) axis, reactive oxygen species (ROS), and apoptotic pathways were conducted using western blot analysis and immunofluorescence.</p><p><strong>Results: </strong>DIS suppressed ErbB4 phosphorylation and downstream Akt signaling, accompanied by the activation of B-cell lymphoma 2/Bcl-2-associated X protein/Caspase-3 (Bcl-2/Bax/Caspase-3) apoptotic pathways after DSCI. Simultaneously, DIS induced a decrease in the mitochondrial membrane potential (ΔΨm) and accumulation of mitochondrial ROS, along with a significant reduction in superoxide dismutase 2 (SOD2) and glutathione peroxidase 4 (GPX4) levels. NaR treatment engaged ErbB4 to restore ErbB4/Akt signaling, inhibited mitochondrial ROS signaling, ameliorated ΔΨm, and reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic neurons, thereby inhibiting neuronal apoptosis. However, the inhibition of ErbB4 phosphorylation along with NaR treatment significantly reversed these therapeutic effects. Furthermore, the pharmacological administration of NaR ameliorated histopathological and neuronal ultrastructural damage in the spinal cord tissues, increased the number of surviving neurons, and facilitated locomotor recovery after DSCI.</p><p><strong>Conclusions: </strong>These findings identify ErbB4 and ROS signaling as key regulators of neuronal survival during DSCI and establish NaR as a candidate therapeutic strategy for DSCI associated with spinal deformity correction surgery.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 8","pages":"51000"},"PeriodicalIF":3.3,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891876","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":"Pharmacological Profile of Purinergic P2Y Receptors Involved in Neurogenic Cardiovascular Modulation Induced by ADP and Related Compounds in Rats.","authors":"Roberto C Silva-Velasco, Kristian A Haanes, Belinda Villanueva-Castillo, Antoinette Maassen van den Brink, Carlos M Villalón","doi":"10.31083/JIN51224","DOIUrl":"https://doi.org/10.31083/JIN51224","url":null,"abstract":"<p><p>Cardiovascular modulation mediated by adenine-based purines is a very complicated and dynamic process driven by adenosine, adenosine diphosphate (ADP), and adenosine triphosphate (ATP). It is orchestrated through the interaction of these molecules with specific purinergic P1, P2Y, and P2X receptors, located throughout the central and peripheral nervous systems. This, along with the constant enzymatic interconversion of these compounds by ectonucleotidases, results in overlapping and highly variable cardiovascular responses. Activation of G protein-coupled purinergic P2Y receptors plays a fundamental role in cardiovascular homeostasis, modulating autonomic integration, neurogenic transmission, and vascular function. Within this context, ADP-sensitive P2Y receptors, particularly the P2Y₁, P2Y₁₂, and P2Y₁₃ subtypes, participate in distinct sensory, autonomic, and functional cardiovascular mechanisms, as identified in several <i>in vitro</i> and <i>in vivo</i> experimental models. Accordingly: (i) the stable and non-hydrolysable ADP analogue, adenosine 5'-O-(β-thio)-diphosphate (ADPβS), has been widely used as a pharmacological tool to investigate P2Y receptor-mediated cardiovascular responses; and (ii) the specific role of P2Y receptors has been confirmed using selective P2Y receptor antagonists, including MRS2500 (P2Y₁), PSB0739 (P2Y₁₂) or MRS2211 (P2Y₁₃). The cardiovascular effects of ADP are complex; depending on the experimental conditions, it can either decrease or increase heart rate, myocardial contractility, vascular tone, and/or systemic blood pressure. These effects are mediated by several P2Y receptors that act at different levels of cardiovascular control, encompassing crucial integration sites within the central nervous system, as well as peripheral autonomic and cardiovascular effector mechanisms such as preganglionic nerves, autonomic ganglia, postganglionic nerves, sensory fibres, vascular smooth muscle, vascular endothelium, and cardiac tissues. In this review, we: (i) summarize the pharmacological profile of the P2Y receptors that mediate cardiovascular responses, with special emphasis on peripheral autonomic, sensory, and vascular mechanisms, revealed in <i>in vivo</i> experimental models; and (ii) highlight the potential of P2Y receptors as therapeutic targets for the treatment of cardiovascular pathologies, including hypertension, coronary vasospasm, ischemic injury, and coagulation problems.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 8","pages":"51224"},"PeriodicalIF":3.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891857","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":"Age-Dependent Effects of Caffeine on Physiological, Behavioral, and Circadian Gene Changes in Young and Mature C57BL/6 Male Mice.","authors":"Sookyoung Park, Zeeshan Ahmad Khan, AbuZar Ansari, Urala Kalasi Apsara Shamali, Anik Kumar Kar, Yejin Lee, Gwangbae Lee, Jaeyeong Kim, Semin Son, Yonggeun Hong","doi":"10.31083/JIN46140","DOIUrl":"https://doi.org/10.31083/JIN46140","url":null,"abstract":"<p><strong>Background: </strong>Caffeine, a widely consumed psychoactive substance, has known effects on physiological and behavioral processes. Recent studies report that caffeine can influence the circadian rhythm, which is linked to many aspects of physiology, energy metabolism, and homeostasis. Therefore, we examined the arousal effects of caffeine via behavioral tests and assessed its impact on the circadian rhythm by measuring clock gene and clock-controlled gene expression in the brains of mice and Neuro 2a (N2a) cells.</p><p><strong>Methods: </strong>Male C57BL/6 mice from two age groups, young (1 month 2 weeks) and mature (10 months 2 weeks), were randomly divided into four subgroups: control, vehicle, caffeine, and caffeine with adenosine (n = 8 each). After inducing fatigue through forced treadmill exercise, we performed balance beam and foot fault tests, and measured the mRNA expression and protein levels of circadian genes (circadian locomotor output cycles kaput (<i>Clock</i>), brain and muscle ARNT-like 1 (<i>Bmal1</i>), period circadian regulator 2 (<i>Per2</i>), cryptochrome circadian regulator 1 (<i>Cry1</i>), and <i>Cry2</i>) in the brain and N2a cells treated with caffeine.</p><p><strong>Results: </strong>Caffeine treatment showed a trend toward reduced body weight gain in both young and mature mice. Behavioral tests indicated improvements in balance and coordination across both age groups. After 16 days of treatment, circadian genes showed significant differences in expression, and adenosine receptor levels changed notably, especially after long-term exposure. In N2a cells, caffeine decreased viability in a dose-dependent manner and affected circadian gene expression.</p><p><strong>Conclusions: </strong>The study demonstrates that caffeine influences body weight, behavior, circadian rhythms, and adenosine receptor protein levels, with age-related variations. These findings deepen the understanding of caffeine's effects on physiological and molecular functions and suggest possible age-specific therapeutic implications or precautions related to caffeine intake.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 8","pages":"46140"},"PeriodicalIF":3.3,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891786","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":"Chronic CeA^CRH Activation Disrupts Colonic IL-22/Reg3g Signaling and Induces Depression-Associated Microbiome Shifts in Male Mice.","authors":"Liaorihong Zhao, Yu Long, Kexin Zeng, Shuya Chen, Tian Qiu, Ou Fu","doi":"10.31083/JIN48170","DOIUrl":"https://doi.org/10.31083/JIN48170","url":null,"abstract":"<p><strong>Background: </strong>Psychological stress shapes brain-body interactions through bidirectionally signaling between central neural circuits and peripheral systems. Central amygdala corticotropin-releasing hormone (CeA^CRH) neurons are key regulators of stress response and immune function. However, their chronic impact on the brain-gut-immune axis and gut microbiota remains poorly understood.</p><p><strong>Methods: </strong>We established a chronic stress model in mice by 14-day chemogenetic activating CRH neurons in the CeA. Behavioral assays were conducted to evaluate anxiety and depressive-like phenotypes. mRNA expression level of cytokines, tight junction proteins and antimicrobial peptide were compared in spleen or colon using qPCR between CeA^CRH activated group and control. In addition, 16S rRNA sequencing was performed to characterize changes in the microbial composition.</p><p><strong>Results: </strong>Chronic activation of CeA^CRH neurons showed a tendency toward anxiety-like behavior and significantly disrupts splenic and colonic immune homeostasis. Notably, the colonic interleukin-22 (IL-22)/regenerating islet‑derived protein 3 gamma (Reg3g) mucosal defense axis was suppressed. Microbiota analysis revealed a shift toward a depression-associated profile, characterized by an increase in potentially pathogenic taxa (e.g., <i>Eggerthella</i> and <i>Actinomycetota</i>) and a reduction in short-chain fatty acid producers (e.g., <i>Ruminococcaceae</i> and <i>Roseburia</i>). These microbial alterations are consistent with clinical observations in patients with depression, supporting the translational relevance of mental disorders and gut microbiota.</p><p><strong>Conclusions: </strong>Chronic activation of CeA^CRH neurons drives coordinated immune, gut barrier, and microbiota alterations, including Claudin-2 upregulation and suppression of the IL-22/Reg3g axis, with IL-22 significantly reduced and Reg3g showing only a decreasing trend. These findings suggest a neuro-immune-microbiota pathway linking central stress circuits to peripheral dysfunction. Targeting IL-22 signaling, epithelial barrier integrity, or microbiota composition may represent promising therapeutic strategies for chronic stress-related disorders.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 8","pages":"48170"},"PeriodicalIF":3.3,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891864","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":"Anticholinergic Burden and Cognitive Function, Depressive Symptoms, and Functional Performance in Individuals With Neurocognitive Disorders: Real-World Evidence.","authors":"Maria Skondra, Leonidas Papadopoulos, Theodora Kougioumtzoglou, Charalampos L Kandilakis, Eleni Konidari, Violeta Papalexiou, Ianthi Marouli, Loukia-Maria Malagkoniari, Andreas Kostakiotis, Theokritos Veskoukis, Vaios Peritogiannis, Polychronis Economou, Panagiotis Felemegkas, Panagiotis Alexopoulos","doi":"10.31083/JIN51135","DOIUrl":"10.31083/JIN51135","url":null,"abstract":"<p><strong>Background: </strong>Despite their negative effects on cognitive function and cognitive decline risk, drugs with anticholinergic properties are commonly prescribed, particularly in older individuals. In this observational study we aimed to shed light on the relationships between anticholinergic burden (ACB) and depressive symptoms and cognitive and functional performance in a real-world clinical setting.</p><p><strong>Methods: </strong>The study included individuals seeking care at the old-age psychiatry outpatient clinic of Patras University Mental Health Services. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale; cognitive function was tapped using the Cognitive Telephone Screening Instrument, the Montreal Cognitive Assessment, and the Mini-Mental State Examination; and functional performance was assessed using the Bristol Activities of Daily Living Scale. Differences in demographic and clinical variables across the four diagnostic groups were analyzed. Regression analyses were performed to examine the associations between ACB, cognitive and non-cognitive symptoms, and demographic variables. In addition, clustering analyses were conducted to identify distinct, naturally occurring examinee subgroups and to assess if ACB differed across them.</p><p><strong>Results: </strong>The study sample consisted of individuals without cognitive impairment (N = 301), people with mild neurocognitive disorder (MiND, N = 264), major neurocognitive disorder caused by Alzheimer's disease (ADMaND, N = 114), or other diseases (nonADMaND, N = 63). Significant associations were detected between ACB and depressive symptoms (0.72, <i>p</i> < 0.001), short-term memory (-0.11, <i>p</i> = 0.017), long-term memory (-0.24, <i>p</i> < 0.001), working memory (-0.24, <i>p</i> = 0.001), attention/concentration (-0.13, <i>p</i> = 0.004), verbal fluency (-0.57, <i>p</i> = 0.003), inductive reasoning (-0.17, <i>p</i> = 0.002), basic activities of daily living (0.29, <i>p</i> = 0.001), and instrumental activities of daily living (0.58, <i>p</i> < 0.001). The clustering analyses indicated that in the cluster including individuals with more advanced cognitive decline, poorer functional status, and more severe depressive symptoms, ACB was higher compared with the second group identified by the analyses (<i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>ACB is related to different aspects of the clinical phenotype of cognitive decline. Despite the lack of solid evidence regarding causal relationships and need for further research, minimizing ACB in clinical settings may embody a potential pragmatic strategy in managing cognitive decline in ageing.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 7","pages":"51135"},"PeriodicalIF":3.3,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620255","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":"Sevoflurane and Aβ_1-42 Oligomers Synergistically Induce Morphological Changes of Astrocytes in the Hippocampus of Male Mice.","authors":"Qinfang Shi, Arpit Kumar Pradhan, Siwei Dong, Gerhard Rammes, Xingxing Wang","doi":"10.31083/JIN50442","DOIUrl":"https://doi.org/10.31083/JIN50442","url":null,"abstract":"<p><strong>Background: </strong>Reactive gliosis serves as a characteristic feature of the pathophysiology of Alzheimer's disease (AD). Nevertheless, the influence of anesthetics on the morphological dynamics of astrocytes remains ambiguous.</p><p><strong>Methods: </strong>Employing <i>ex vivo</i> hippocampal slices, in this study, we explored the impacts of sevoflurane and Amyloid-β peptide 1-42 (Aβ_1-42) oligomers on astrocytic morphology. The primary outcomes encompassed the fluorescence intensity of glial fibrillary acidic protein (GFAP), the levels of a 38-kDa GFAP breakdown product (a marker of astroglial injury), and quantitative morphometric analyses (cell volume, surface area, branch complexity, and Sholl intersections).</p><p><strong>Results: </strong>Co-exposure to sevoflurane and Aβ_1-42 led to an elevation of the 38-kDa GFAP breakdown product and a significant reduction in the mean fluorescence intensity of GFAP. Moreover, it resulted in a decrease in astrocytic volume, surface area, branch complexity, and Sholl intersections. These synergistic alterations were not observed when either treatment was administered alone.</p><p><strong>Conclusions: </strong>These findings imply that sevoflurane aggravates Aβ_1-42-induced astrocytic dysfunction, which has implications for perioperative management in patients with AD or those at risk of developing AD.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 7","pages":"50442"},"PeriodicalIF":3.3,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620439","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":"Sarsasapogenin Improves Pathological Phenotypes in MPTP/MPP⁺-Induced Parkinson's Disease Models: Synergistic Actions of Neurite Outgrowth, Neurotransmitter Modulation, and Anti-Inflammation.","authors":"Wendi Deng, Jinfeng Hong, Weixia Li, Yi Zhang, Yongping Zhang, Zhiyou Yang","doi":"10.31083/JIN50683","DOIUrl":"https://doi.org/10.31083/JIN50683","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a prevalent neurodegenerative disorder hallmarked by progressive loss of midbrain dopaminergic (DA) neurons, neurite atrophy, neurotransmitter imbalance, and motor dysfunction. Therapeutic strategies targeting neuronal integrity and neuroinflammation hold translational value beyond conventional symptomatic therapies for PD. Sarsasapogenin, a natural steroidal saponin, exhibits documented neuroprotective properties in multiple neurological diseases. However, its therapeutic potential and underlying mechanisms in PD remain to be elucidated.</p><p><strong>Methods: </strong>The neuroprotective efficacy of sarsasapogenin was assessed in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse PD model and 1-methyl-4-phenylpyridinium ion (MPP⁺)-insulted primary cortical and dopaminergic neuronal cultures. Motor function was evaluated via a variety of behavioral tests. Survival of dopaminergic neurons was quantified using tyrosine hydroxylase (TH) immunostaining. Levels of monoamine neurotransmitters and their metabolites were measured using high-performance liquid chromatography (HPLC), while serum proinflammatory cytokines were determined using enzyme-linked immunosorbent assay (ELISA). Neurite outgrowth and neuronal viability were examined under both preventive and therapeutic treatment regimens <i>in vitro</i>. Potential molecular targets of sarsasapogenin were screened and identified via Drug Affinity Responsive Target Stability (DARTS) coupled with molecular docking.</p><p><strong>Results: </strong>Twenty-one-day sarsasapogenin intervention mitigated aberrant motor deficits in MPTP-treated mice, rescued TH⁺ dopaminergic neurons in the substantia nigra, restored homeostasis of dopamine and norepinephrine, normalized the turnover of monoamines, and decreased peripheral levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). In primary neuronal cultures, sarsasapogenin significantly ameliorated MPP⁺-triggered neurite atrophy and neuronal loss in both cortical and ventral mesencephalic dopaminergic neurons. DARTS screening combined with molecular docking identified serpin family H member 1 (Serpin) H1 as a candidate binding protein of sarsasapogenin, with a favorable binding affinity of -8.6 kcal/mol.</p><p><strong>Conclusions: </strong>Sarsasapogenin exerts comprehensive neuroprotective effects in preclinical PD models via synergistic modulation of dopaminergic neuronal survival, neurotransmitter balance, inflammatory inhibition, and neurite outgrowth. These findings highlight sarsasapogenin as a promising multi-target candidate for PD intervention, whereas the precise functional role of Serpin H1 in mediating its neuroprotective actions warrants further in-depth investigation.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 7","pages":"50683"},"PeriodicalIF":3.3,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620371","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":"The Efficacy of Experimental Therapy for Stroke Induced by Cerebral Air Embolism in Awake Rats Is Affected by Heliox Inhalation Temperature.","authors":"Arina Kholina, Alina Ismailova, Victor Palikov, Natalya Borozdina, Sergey Kozlov, Olga Patsap, Michael Ignatyuk, Dmitry Rzhevsky, Gulsara Slashcheva, Elvira Shaykhutdinova, Igor Dyachenko, Arkady Murashev, Nikolay Pavlov, Victor Baranov","doi":"10.31083/JIN51502","DOIUrl":"https://doi.org/10.31083/JIN51502","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have shown that Heliox, a mixture of 32% oxygen and 68% helium administered at a warm temperature, is effective in treating ischemic brain injury caused by cerebral arterial air embolism. At the same time, therapeutic hypothermia has been shown to lead to a favorable neurological outcome in patients in the acute phase of ischemic stroke; however, there are no published data on the use of Heliox at room temperature after ischemic stroke. All published data indicate only the efficacy of heated Heliox. The most effective temperature regimen for Heliox inhalation to prevent neurological deficits in stroke remains unknown.</p><p><strong>Methods: </strong>Three Heliox inhalation temperature regimens were studied at 20-22 °C, 40-50 °C, and 60-70 °C. The mixture was administered immediately after inducing ischemic stroke in awake rats using a model of cerebral arterial air embolism. Respiratory and cardiovascular function, as well as body temperature, coordination, muscle strength, and serum calcium binding protein B (S100B) concentrations were studied 24 hours after embolization. A brain histopathological study was also performed.</p><p><strong>Results: </strong>Inhalation of heated Heliox (40-50 °C and 60-70 °C) immediately after cerebral arterial air embolism was shown to be an effective method for maintaining respiratory and cardiovascular function and body temperature, for preventing the development of foci of ischemic brain damage on 2,3,5-triphenyltetrazolium chloride (TTC)-stained sections of the brain, and for partially preserving coordination, muscle strength, locomotor activity, and for a partial reduction in serum S100B concentration during the acute phase of ischemic stroke in rats compared to the untreated group with cerebral arterial air embolism (CAE). Unheated Heliox had a negative effect on experimental animals, and decreased a survival rate to 62.5%.</p><p><strong>Conclusions: </strong>Heated Heliox has an equally positive effect at temperatures of 40-50 °C and 60-70 °C, and significantly alleviated the symptoms of ischemic stroke during the acute phase. In contrast, unheated Heliox at room temperature (20-22 °C) had a negative effect on the course of ischemic stroke in rats.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 7","pages":"51502"},"PeriodicalIF":3.3,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620412","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":"Evaluation of the Behavioral and Histopathological Outcomes of Two Cuprizone Administration Routes in a Mouse Model of Multiple Sclerosis.","authors":"Kholoud M Al-Otaibi","doi":"10.31083/JIN52589","DOIUrl":"https://doi.org/10.31083/JIN52589","url":null,"abstract":"<p><strong>Background: </strong>The cuprizone (CPZ) model has been used to study de- and re-myelination in mice; Previous studies have used different routes for CPZ intoxication, but the results were highly variable.</p><p><strong>Methods: </strong>Here, we compared demyelination induced by the administration of 0.3% CPZ mixed with ground rodent chow and a 400 mg/kg CPZ suspension in carboxymethyl cellulose (CMC) via oral gavage in SWR/J mice. The mice were assigned into a control group, a CPZ diet group, and an oral CPZ groups (n = 6 mice/group). Rotarod, hanging wire, and open field tests were performed to evaluate locomotor activity. Histological analyses were conducted on the corpus callosum (CC) of the brain to determine myelin loss and on the liver to assess the toxicity of CPZ.</p><p><strong>Results: </strong>The administration of CPZ with ground rodent chow significantly reduced body weight gains, grip strength, and motor coordination performance during the 5-week demyelination period. In contrast, all analyzed parameters were less different in mice receiving CPZ via oral gavage. However, both CPZ routes significantly reduced myelin content in the CC. Additionally, the oral administration of CPZ had strong effects on liver toxicity compared to that of CPZ diet feeding. This study showed that both routes of CPZ intoxication could induce reproducible and consistent demyelination changes within the CC of the mouse brain, with the CPZ diet being more effective based on all analytical parameters and having fewer toxic effects on the liver compared with oral CPZ.</p><p><strong>Conclusions: </strong>In conclusion, the resultsassist in the selection of a suitable multiple sclerosis (MS) model for investigating disease mechanisms and therapies.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 7","pages":"52589"},"PeriodicalIF":3.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620318","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":"Extracellular Vesicle-Mediated Delivery of VEGF and NGF Protects Dopaminergic Neurons in 6-OHDA-Induced Parkinson's Disease Models.","authors":"Wenyu Yan, Xianyue Meng, Yan Wang, Chuanfei Wei, Fabin Han, Xueli Li","doi":"10.31083/JIN50932","DOIUrl":"https://doi.org/10.31083/JIN50932","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a neurodegenerative disorder marked by motor dysfunction. No definitive methods exist to repair damaged neurons. Vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) are two neuroprotective agents that work synergistically. However, these large molecular proteins have difficulty crossing the blood-brain barrier (BBB). Extracellular vesicles (EVs) offer superior targeting and low immunogenicity, making them excellent carriers. In this study we examined the protective effects of VEGF and NGF in a cell model and evaluated the therapeutic potential of VEGF-NGF contained within EVs in PD rats.</p><p><strong>Methods: </strong>EVs were isolated using sequential differential centrifugation and characterized using transmission electron microscopy, nanoparticle tracking analysis, and western blotting (WB). VEGF and NGF were loaded into the EVs using a saponin-assisted method to create VEGF@EVs, NGF@EVs, and VEGF/NGF@EVs. The viability of 6-hydroxydopamine hydrochloride (6-OHDA)-induced SH-SY5Y cells was measured using the cell counting kit-8 assay before and after treatment with VEGF and NGF. Autophagy levels were assessed using WB, and the role of autophagy was further explored using the autophagy inhibitor chloroquine. Unilateral PD rat models were established via stereotactic injection of 6-OHDA into male Sprague-Dawley rats. Behavioral changes were monitored before and after treatment. Neuronal recovery, neurotransmitter levels, and autophagy levels in the rat brains were evaluated using immunohistochemistry, enzyme-linked immunosorbent assay, and WB.</p><p><strong>Results: </strong>VEGF/NGF@EVs significantly enhanced the viability of 6-OHDA-induced SH-SY5Y cells. A complete autophagic process was identified as essential for this protective effect. The intranasal administration of VEGF/NGF@EVs improved motor behavior in PD rats, with performance better than that of single growth factor treatments. The number of tyrosine hydroxylase (TH)-positive neurons, TH protein expression, and dopamine content were significantly increased. In addition, the level of autophagy in the rat substantia nigra was elevated.</p><p><strong>Conclusions: </strong>VEGF/NGF@EVs exert protective effects in both <i>in vitro</i> and <i>in vivo</i> 6-OHDA-induced PD models by promoting autophagy, demonstrating greater efficacy than either growth factor alone. By transplanting VEGF/NGF@EVs into PD rats, we showed that these vesicles can effectively cross the BBB and deliver targeted therapy to the central nervous system. This study highlights the significant potential of EV-mediated protein transplantation strategies for treating neurological disorders.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 7","pages":"50932"},"PeriodicalIF":3.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620320","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}