Pub Date : 2025-02-01DOI: 10.1016/j.brainresbull.2025.111198
Xiaoting Luo , Junyi Liang , Xue Lei , Fengqi Sun , Minghai Gong , Bin Liu , Zhongguang Zhou
Alzheimer's disease (AD) stands as one of the most prevalent neurodegenerative disorders, characterized by a progressive decline in cognitive function, neuroinflammation, amyloid-beta (Aβ) plaques, and neurofibrillary tangles (NFTs). With the global aging population, the incidence of AD continues to rise, yet current therapeutic strategies remain limited in their ability to significantly alleviate cognitive impairments. Therefore, a deeper understanding of the molecular mechanisms underlying AD is imperative for the development of more effective treatments. In recent years, the transcription factor C/EBPβ has emerged as a pivotal regulator in several pathological processes of AD, including neuroinflammation, lipid metabolism, Aβ processing, and tau phosphorylation. Through intricate post-translational modifications, C/EBPβ modulates these processes and may influence the progression of AD on multiple fronts. This review systematically explores the multifaceted roles of C/EBPβ in the pathogenesis of AD, delving into its crucial involvement in neuroinflammation, Aβ production, tau pathology, and lipid metabolism dysregulation. Furthermore, we critically assess therapeutic strategies targeting C/EBPβ, examining the challenges and opportunities in regulating this factor. By synthesizing the latest research findings, we offer a more comprehensive understanding of the role of C/EBPβ in AD and discuss its potential as a therapeutic intervention target.
{"title":"C/EBPβ in Alzheimer’s disease: An integrative regulator of pathological mechanisms","authors":"Xiaoting Luo , Junyi Liang , Xue Lei , Fengqi Sun , Minghai Gong , Bin Liu , Zhongguang Zhou","doi":"10.1016/j.brainresbull.2025.111198","DOIUrl":"10.1016/j.brainresbull.2025.111198","url":null,"abstract":"<div><div>Alzheimer's disease (AD) stands as one of the most prevalent neurodegenerative disorders, characterized by a progressive decline in cognitive function, neuroinflammation, amyloid-beta (Aβ) plaques, and neurofibrillary tangles (NFTs). With the global aging population, the incidence of AD continues to rise, yet current therapeutic strategies remain limited in their ability to significantly alleviate cognitive impairments. Therefore, a deeper understanding of the molecular mechanisms underlying AD is imperative for the development of more effective treatments. In recent years, the transcription factor C/EBPβ has emerged as a pivotal regulator in several pathological processes of AD, including neuroinflammation, lipid metabolism, Aβ processing, and tau phosphorylation. Through intricate post-translational modifications, C/EBPβ modulates these processes and may influence the progression of AD on multiple fronts. This review systematically explores the multifaceted roles of C/EBPβ in the pathogenesis of AD, delving into its crucial involvement in neuroinflammation, Aβ production, tau pathology, and lipid metabolism dysregulation. Furthermore, we critically assess therapeutic strategies targeting C/EBPβ, examining the challenges and opportunities in regulating this factor. By synthesizing the latest research findings, we offer a more comprehensive understanding of the role of C/EBPβ in AD and discuss its potential as a therapeutic intervention target.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111198"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.brainresbull.2025.111214
Yifan Lai , Jiawei Qiu , Kuang Zheng , Xiang Li , Yinuo Lin , Zhengzheng Li , Haiqiu Sun
Hearing loss is a pervasive issue affecting numerous individuals, and its etiology and categorization are multifaceted. Among these, sensorineural hearing loss (SNHL) emerges as the most prevalent variant among these. The primary causative factor underlying SNHL resides in the depletion of auditory hair cells within the cochlea, yet the pursuit of efficacious therapeutic interventions remains an ongoing challenge. Previous investigations have illuminated the role of mitochondrial dysfunction in precipitating cellular apoptosis, and mitophagy has emerged as a promising mechanism to ameliorate such dysfunction. Additionally, it has been noted that metformin possesses the specific ability to induce mitophagy. Herein, our objective is to explore the protective effects of metformin-induced mitophagy against apoptosis in auditory hair cells (HEI-OC1 cells) and explore its potential mechanisms. Our results revealed that metformin effectively triggered mitophagy in HEI-OC1 cells. Moreover, metformin treatment showed the ability to prevent tert-butyl hydroperoxide (TBHP) induced mitochondrial dysfunction and intrinsic apoptotic pathways. Mechanistically, we discovered that metformin activates AMP-activated protein kinase (AMPK) signaling in HEI-OC1 cells stimulated by TBHP, thereby triggering mitophagy. Overall, our results suggest that metformin may represent a promising and innovative therapeutic strategy for mitigating the onset of hearing loss.
{"title":"Metformin-induced mitophagy suppresses auditory hair cell apoptosis via AMPK pathway","authors":"Yifan Lai , Jiawei Qiu , Kuang Zheng , Xiang Li , Yinuo Lin , Zhengzheng Li , Haiqiu Sun","doi":"10.1016/j.brainresbull.2025.111214","DOIUrl":"10.1016/j.brainresbull.2025.111214","url":null,"abstract":"<div><div>Hearing loss is a pervasive issue affecting numerous individuals, and its etiology and categorization are multifaceted. Among these, sensorineural hearing loss (SNHL) emerges as the most prevalent variant among these. The primary causative factor underlying SNHL resides in the depletion of auditory hair cells within the cochlea, yet the pursuit of efficacious therapeutic interventions remains an ongoing challenge. Previous investigations have illuminated the role of mitochondrial dysfunction in precipitating cellular apoptosis, and mitophagy has emerged as a promising mechanism to ameliorate such dysfunction. Additionally, it has been noted that metformin possesses the specific ability to induce mitophagy. Herein, our objective is to explore the protective effects of metformin-induced mitophagy against apoptosis in auditory hair cells (HEI-OC1 cells) and explore its potential mechanisms. Our results revealed that metformin effectively triggered mitophagy in HEI-OC1 cells. Moreover, metformin treatment showed the ability to prevent tert-butyl hydroperoxide (TBHP) induced mitochondrial dysfunction and intrinsic apoptotic pathways. Mechanistically, we discovered that metformin activates AMP-activated protein kinase (AMPK) signaling in HEI-OC1 cells stimulated by TBHP, thereby triggering mitophagy. Overall, our results suggest that metformin may represent a promising and innovative therapeutic strategy for mitigating the onset of hearing loss.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111214"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Subcortical vascular mild cognitive impairment (svMCI) frequently occurs alongside depression symptoms, significantly affecting patients' quality of life. While cognitive decline and depression symptoms are linked to cerebellar changes, the specific relationship between these changes and cognitive status in svMCI patients with depression symptoms remains unclear.
Objective
This study aimed to investigates the gray matter volume and functional alterations in the cerebellum of svMCI patients, with and without depression symptoms, and their correlation with cognitive and depressive symptoms.
Methods
We enrolled 16 svMCI patients with depression symptoms (svMCI+D), 15 without (svMCI-D), and 12 normal controls (NC). Multimodal MRI scans were conducted, assessing gray matter volume and resting-state functional connectivity (RSFC) in the cerebellum. Correlations between RSFC and clinical scores from the Montreal Cognitive Assessment (MoCA) and Hamilton Depression Scale (HAMD) were analyzed.
Results
Structural analysis indicated gray matter atrophy in left cerebellar lobules I_IV and VI (Cere6.L) in svMCI patients. svMCI+D patients showed reduced RSFC between Cere6.L and left cerebellar region IX and the left superior frontal gyrus (SFGdor.L). Both svMCI+D and svMCI-D groups showed increased RSFC between Cere6.L and the right caudate nucleus. RSFC between Cere6.L and SFGdor.L correlated negatively with HAMD scores in svMCI+D and positively with MoCA scores in svMCI-D. RSFC between Cere6.L and the right caudate nucleus also correlated positively with MoCA in the svMCI-D.
Conclusion
Cerebellar abnormalities, including the gray matter atrophy and RSFC changes, are associated with svMCI, particularly when depression symptoms are present. These results suggest potential diagnostic and therapeutic implications for svMCI and emphasize the need for further research on the cerebellum's role in cognitive and emotional disorders.
{"title":"Cerebellum abnormalities in vascular mild cognitive impairment with depression symptom patients: A multimodal magnetic resonance imaging study","authors":"Yirong Chen , Liling Chen , Liyu Hu , Jianjun Wang , Jinhuan Zhang , Hanqing Lyu , Jinping Xu , Jianxiang Chen , Haibo Yu","doi":"10.1016/j.brainresbull.2025.111213","DOIUrl":"10.1016/j.brainresbull.2025.111213","url":null,"abstract":"<div><h3>Background</h3><div>Subcortical vascular mild cognitive impairment (svMCI) frequently occurs alongside depression symptoms, significantly affecting patients' quality of life. While cognitive decline and depression symptoms are linked to cerebellar changes, the specific relationship between these changes and cognitive status in svMCI patients with depression symptoms remains unclear.</div></div><div><h3>Objective</h3><div>This study aimed to investigates the gray matter volume and functional alterations in the cerebellum of svMCI patients, with and without depression symptoms, and their correlation with cognitive and depressive symptoms.</div></div><div><h3>Methods</h3><div>We enrolled 16 svMCI patients with depression symptoms (svMCI+D), 15 without (svMCI-D), and 12 normal controls (NC). Multimodal MRI scans were conducted, assessing gray matter volume and resting-state functional connectivity (RSFC) in the cerebellum. Correlations between RSFC and clinical scores from the Montreal Cognitive Assessment (MoCA) and Hamilton Depression Scale (HAMD) were analyzed.</div></div><div><h3>Results</h3><div>Structural analysis indicated gray matter atrophy in left cerebellar lobules I_IV and VI (Cere6.L) in svMCI patients. svMCI+D patients showed reduced RSFC between Cere6.L and left cerebellar region IX and the left superior frontal gyrus (SFGdor.L). Both svMCI+D and svMCI-D groups showed increased RSFC between Cere6.L and the right caudate nucleus. RSFC between Cere6.L and SFGdor.L correlated negatively with HAMD scores in svMCI+D and positively with MoCA scores in svMCI-D. RSFC between Cere6.L and the right caudate nucleus also correlated positively with MoCA in the svMCI-D.</div></div><div><h3>Conclusion</h3><div>Cerebellar abnormalities, including the gray matter atrophy and RSFC changes, are associated with svMCI, particularly when depression symptoms are present. These results suggest potential diagnostic and therapeutic implications for svMCI and emphasize the need for further research on the cerebellum's role in cognitive and emotional disorders.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111213"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.brainresbull.2025.111220
Wei Luo , Meiyi Duan , Enpeng Liang , Siwei Wang , Jie Yuan
The sleep-wake states and general anesthesia share many neurophysiological similarities, as both involve reversible changes in consciousness and modulation of brain activity. This paper reviews the role of glutamatergic neurons, the brain's primary excitatory neurons, in regulating sleep-wake states and general anesthesia. We discuss the involvement of glutamatergic neurons across various brain regions, including the brainstem, basal forebrain, thalamus, hypothalamus, and cortex, highlighting their contributions to physiological sleep-wake and anesthesia modulation. Recent advancements in techniques such as optogenetics, chemogenetics, and neural tracing have enhanced our understanding of these neurons' functions. Understanding these mechanisms can lead to improved therapeutic strategies for sleep disorders and more precise anesthetic practices, providing new avenues for clinical intervention.
{"title":"The regulation of glutamatergic nervous system in sleep-wake states and general anesthesia","authors":"Wei Luo , Meiyi Duan , Enpeng Liang , Siwei Wang , Jie Yuan","doi":"10.1016/j.brainresbull.2025.111220","DOIUrl":"10.1016/j.brainresbull.2025.111220","url":null,"abstract":"<div><div>The sleep-wake states and general anesthesia share many neurophysiological similarities, as both involve reversible changes in consciousness and modulation of brain activity. This paper reviews the role of glutamatergic neurons, the brain's primary excitatory neurons, in regulating sleep-wake states and general anesthesia. We discuss the involvement of glutamatergic neurons across various brain regions, including the brainstem, basal forebrain, thalamus, hypothalamus, and cortex, highlighting their contributions to physiological sleep-wake and anesthesia modulation. Recent advancements in techniques such as optogenetics, chemogenetics, and neural tracing have enhanced our understanding of these neurons' functions. Understanding these mechanisms can lead to improved therapeutic strategies for sleep disorders and more precise anesthetic practices, providing new avenues for clinical intervention.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111220"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.brainresbull.2025.111226
Yuyu An , Shanshan Cao , Leilei Shi , Yuhan Zhang , Xin Wang , Shiyu Yuan , Yongheng Shi , Bin Wang , Jiping Liu , Chao-jun Han
Diabetic neuropathic pain (DNP) is a common complication of diabetes mellitus (DM) and is characterized by spontaneous pain and neuroinflammation. The Sigma-1 receptor (Sig-1R) has been proposed as a target for analgesic development. It is an important receptor with anti-inflammatory properties and has been found to regulate DNP. However, it is not known whether Sig-1R can ameliorate pathological neuroinflammation in DNP. The present study used a rat model of DNP and a highly selective agonist of Sig-1R to assess the effects of the protein on neuropathic pain in rats with type 2 diabetes mellitus. The rats were divided into Control, Model, Sig-1R agonist PRE-084 (0.3, 0.6, 1 mg/kg), and metformin (Met, 20 mg/kg) groups, with seven rats per group, and their body weight, fasting blood glucose, mechanical withdrawal threshold and thermal withdrawal latency were tested weekly for two weeks. After treatment with PRE-084, the pain thresholds in the DNP rats were significantly improved, together with pathological changes in the dorsal root ganglion, reductions in the serum levels of TNF-α, IL-1β, IL-6, MOD, and prostaglandin E2 (PGE2), and the activity of superoxide dismutase was increased. The mRNA levels of TNF-α, IL-1β, and cyclooxygenase 2 (COX-2) were reduced. Pharmacological inhibition of Sig-1R with BD1047 (10 μM) abolished Sig-1R-mediated activation of lipopolysaccharide-treated BV-2 microglial cells. It was also found that PRE-084 increased phosphorylation of serine/threonine protein kinase B (AKT) and glycogen synthase kinase 3β (GSK-3β) at Ser9, inhibiting nuclear factor kappa B (NF-κB)-mediated neuroinflammation in the dorsal root ganglion, thus reducing DNP. The findings suggest that the effect of Sig-1R agonist PRE-084 on DNP may reduce the level of inflammation through the up-regulation of AKT/GSK-3β and down-regulation of the NF-κB signaling, thereby contributing to the treatment of the disease.
{"title":"Pharmacological modulation of Sigma-1 receptor ameliorates pathological neuroinflammation in rats with diabetic neuropathic pain via the AKT/GSK-3β/NF-κB pathway","authors":"Yuyu An , Shanshan Cao , Leilei Shi , Yuhan Zhang , Xin Wang , Shiyu Yuan , Yongheng Shi , Bin Wang , Jiping Liu , Chao-jun Han","doi":"10.1016/j.brainresbull.2025.111226","DOIUrl":"10.1016/j.brainresbull.2025.111226","url":null,"abstract":"<div><div>Diabetic neuropathic pain (DNP) is a common complication of diabetes mellitus (DM) and is characterized by spontaneous pain and neuroinflammation. The Sigma-1 receptor (Sig-1R) has been proposed as a target for analgesic development. It is an important receptor with anti-inflammatory properties and has been found to regulate DNP. However, it is not known whether Sig-1R can ameliorate pathological neuroinflammation in DNP. The present study used a rat model of DNP and a highly selective agonist of Sig-1R to assess the effects of the protein on neuropathic pain in rats with type 2 diabetes mellitus. The rats were divided into Control, Model, Sig-1R agonist PRE-084 (0.3, 0.6, 1 mg/kg), and metformin (Met, 20 mg/kg) groups, with seven rats per group, and their body weight, fasting blood glucose, mechanical withdrawal threshold and thermal withdrawal latency were tested weekly for two weeks. After treatment with PRE-084, the pain thresholds in the DNP rats were significantly improved, together with pathological changes in the dorsal root ganglion, reductions in the serum levels of TNF-α, IL-1β, IL-6, MOD, and prostaglandin E2 (PGE2), and the activity of superoxide dismutase was increased. The mRNA levels of TNF-α, IL-1β, and cyclooxygenase 2 (COX-2) were reduced. Pharmacological inhibition of Sig-1R with BD1047 (10 μM) abolished Sig-1R-mediated activation of lipopolysaccharide-treated BV-2 microglial cells. It was also found that PRE-084 increased phosphorylation of serine/threonine protein kinase B (AKT) and glycogen synthase kinase 3β (GSK-3β) at Ser9, inhibiting nuclear factor kappa B (NF-κB)-mediated neuroinflammation in the dorsal root ganglion, thus reducing DNP. The findings suggest that the effect of Sig-1R agonist PRE-084 on DNP may reduce the level of inflammation through the up-regulation of AKT/GSK-3β and down-regulation of the NF-κB signaling, thereby contributing to the treatment of the disease.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111226"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.brainresbull.2025.111204
Fengxia Yu , Dong Liu , Xia Ma , Yawen Liu , Linkun Cai , Erwei Zhao , Zixu Huang , Zhe Zhang , Tingting Zhang , PengGang Qiao , Wei Zheng , Chunyan Guo , Linxue Qian , Pengling Ren , Zhenchang Wang
Purpose
Dobutamine, a sympathomimetic agent, is widely used clinically, influencing cardiac output, heart rate (HR), and blood pressure (BP), which may impact cerebral blood flow (CBF), critical for brain metabolism. However, the effects of dobutamine on CBF and internal carotid artery (ICA) blood flow remain unclear, with contradictory reported in both clinical and animal studies. It is necessary to investigate the effects of dobutamine on cervical and cerebral hemodynamics. This study aimed to evaluate the effects of dobutamine infusion on ICA blood flow and CBF, explore their relationship, and identify factors influencing CBF to facilitate timely monitoring in clinical practice.
Methods
Forty-eight healthy volunteers underwent physiological assessment, ICA ultrasound, and brain magnetic resonance imaging (MRI) data before and after the administration of dobutamine. Paired t and Wilcoxon signed-rank tests were used to analyze changes, while logistic regression explored associations between hemodynamic factors and CBF.
Results
Dobutamine infusion significantly increased HR, respiration rate, systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure, while blood oxygen remained stable. Compared with those in the resting state, the peak systolic velocity (Vs), resistance index, pulsatility index, and systolic/diastolic ratio (S/D) increased, whereas end-diastolic velocity (Vd) decreased. ICA diameter and mean velocity showed no significant changes. CBF significantly decreased in the anterior and middle cerebral arteries. Logistic regression identified SBP, DBP, and S/D difference as key factors associated with CBF reduction.
Conclusions
Dobutamine altered ICA hemodynamics and reduced CBF in anterior and middle cerebral arteries. Real-time ICA ultrasound monitoring provides valuable guidance during clinical use.
{"title":"Dobutamine-induced alterations in internal carotid artery blood flow and cerebral blood flow in healthy adults","authors":"Fengxia Yu , Dong Liu , Xia Ma , Yawen Liu , Linkun Cai , Erwei Zhao , Zixu Huang , Zhe Zhang , Tingting Zhang , PengGang Qiao , Wei Zheng , Chunyan Guo , Linxue Qian , Pengling Ren , Zhenchang Wang","doi":"10.1016/j.brainresbull.2025.111204","DOIUrl":"10.1016/j.brainresbull.2025.111204","url":null,"abstract":"<div><h3>Purpose</h3><div>Dobutamine, a sympathomimetic agent, is widely used clinically, influencing cardiac output, heart rate (HR), and blood pressure (BP), which may impact cerebral blood flow (CBF), critical for brain metabolism. However, the effects of dobutamine on CBF and internal carotid artery (ICA) blood flow remain unclear, with contradictory reported in both clinical and animal studies. It is necessary to investigate the effects of dobutamine on cervical and cerebral hemodynamics. This study aimed to evaluate the effects of dobutamine infusion on ICA blood flow and CBF, explore their relationship, and identify factors influencing CBF to facilitate timely monitoring in clinical practice.</div></div><div><h3>Methods</h3><div>Forty-eight healthy volunteers underwent physiological assessment, ICA ultrasound, and brain magnetic resonance imaging (MRI) data before and after the administration of dobutamine. Paired t and Wilcoxon signed-rank tests were used to analyze changes, while logistic regression explored associations between hemodynamic factors and CBF.</div></div><div><h3>Results</h3><div>Dobutamine infusion significantly increased HR, respiration rate, systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure, while blood oxygen remained stable. Compared with those in the resting state, the peak systolic velocity (Vs), resistance index, pulsatility index, and systolic/diastolic ratio (S/D) increased, whereas end-diastolic velocity (Vd) decreased. ICA diameter and mean velocity showed no significant changes. CBF significantly decreased in the anterior and middle cerebral arteries. Logistic regression identified SBP, DBP, and S/D difference as key factors associated with CBF reduction.</div></div><div><h3>Conclusions</h3><div>Dobutamine altered ICA hemodynamics and reduced CBF in anterior and middle cerebral arteries. Real-time ICA ultrasound monitoring provides valuable guidance during clinical use.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111204"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.brainresbull.2025.111203
Hongbo Jiang , Xunling Wang , Yingwei Liang , Yinghan Hou , Xinping Yue , Zhiyi Zhang , Dan Chen , Xinyi Fan , Ailin Du
Objective
This study aimed to investigate the effect of aminooxyacetic acid (AOAA) on cognitive function, particularly learning and memory, in a rat model of chronic alcoholism. Additionally, the study explored changes in cystathionine β-synthase (CBS), hydrogen sulfide (H₂S), and serotonin (5-HT) levels in the prefrontal cortex to understand the potential neurochemical mechanisms involved.
Methods
Sixty-four male SD rats were randomly divided into four groups, with 16 rats in each: Con, Con + AOAA, Model, and Model + AOAA. The Model group received a 6 % ethanol solution for 28 days. From day 14, the Model + AOAA group was treated with daily intraperitoneal injections of AOAA (5 mg/kg) for 14 consecutive days. Cognitive function was assessed using the Morris water maze, mitochondrial function was evaluated through ATPase activity, and H₂S levels were measured. CBS and 5-HT levels in the prefrontal cortex were analyzed by immunohistochemistry.
Results
Compared to the control groups, rats in the Model group exhibited significant impairments in learning and memory, increased CBS expression, elevated H₂S levels, and decreased 5-HT release. AOAA treatment improved memory performance, reduced CBS expression and H₂S levels, and increased 5-HT release, although these measures did not fully return to baseline. No significant differences were observed between the two control groups.
Conclusion
AOAA may alleviate cognitive deficits associated with chronic alcoholism by inhibiting CBS expression, reducing H₂S levels, and enhancing 5-HT release in the prefrontal cortex. These findings suggest AOAA as a potential therapeutic strategy for alcohol-induced cognitive impairments.
{"title":"Effects of aminooxyacetic acid on learning and memory function and neurochemical changes in chronic alcoholism","authors":"Hongbo Jiang , Xunling Wang , Yingwei Liang , Yinghan Hou , Xinping Yue , Zhiyi Zhang , Dan Chen , Xinyi Fan , Ailin Du","doi":"10.1016/j.brainresbull.2025.111203","DOIUrl":"10.1016/j.brainresbull.2025.111203","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the effect of aminooxyacetic acid (AOAA) on cognitive function, particularly learning and memory, in a rat model of chronic alcoholism. Additionally, the study explored changes in cystathionine β-synthase (CBS), hydrogen sulfide (H₂S), and serotonin (5-HT) levels in the prefrontal cortex to understand the potential neurochemical mechanisms involved.</div></div><div><h3>Methods</h3><div>Sixty-four male SD rats were randomly divided into four groups, with 16 rats in each: Con, Con + AOAA, Model, and Model + AOAA. The Model group received a 6 % ethanol solution for 28 days. From day 14, the Model + AOAA group was treated with daily intraperitoneal injections of AOAA (5 mg/kg) for 14 consecutive days. Cognitive function was assessed using the Morris water maze, mitochondrial function was evaluated through ATPase activity, and H₂S levels were measured. CBS and 5-HT levels in the prefrontal cortex were analyzed by immunohistochemistry.</div></div><div><h3>Results</h3><div>Compared to the control groups, rats in the Model group exhibited significant impairments in learning and memory, increased CBS expression, elevated H₂S levels, and decreased 5-HT release. AOAA treatment improved memory performance, reduced CBS expression and H₂S levels, and increased 5-HT release, although these measures did not fully return to baseline. No significant differences were observed between the two control groups.</div></div><div><h3>Conclusion</h3><div>AOAA may alleviate cognitive deficits associated with chronic alcoholism by inhibiting CBS expression, reducing H₂S levels, and enhancing 5-HT release in the prefrontal cortex. These findings suggest AOAA as a potential therapeutic strategy for alcohol-induced cognitive impairments.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111203"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.brainresbull.2025.111219
Xiaoming Zhang , Yibing Guo , Kun Fang , Xiangqian Huang , Duo Lan , Mengqi Wang , Lina Jia , Xunming Ji , Ran Meng , Da Zhou
Background
Ischemic stroke (IS) remains a significant global health burden, necessitating the development of novel therapeutic strategies. This study aims to systematically evaluate the therapeutic effects of mesenchymal stem cell-derived exosomes (MSC-Exos) on IS outcomes in rodent models.
Methods
A comprehensive literature search was conducted across multiple databases to identify studies investigating the effects of MSC-Exos on rodent models of IS. Following rigorous inclusion and exclusion criteria, 73 high-quality studies were selected for meta-analysis. Primary outcomes included reductions in infarct volume/ratio and improvements in functional recovery scores. Data extraction and analysis were performed using RevMan 5.3 software.
Results
Pooled data indicated that MSC-Exos administration significantly reduced infarct size and improved functional recovery scores in rodent models of IS. Treatment within 24 hours and beyond 24 hours of stroke induction both demonstrated substantial reductions in infarct volume/ratio compared to controls. Furthermore, MSC-Exos-treated groups exhibited marked improvements in functional recovery, as assessed by various neurobehavioral tests. The meta-analysis showed no significant publication bias, and heterogeneity levels were acceptable.
Conclusions
MSC-Exos reveal significant therapeutic potential for IS, with evidence supporting their efficacy in reducing infarct size and enhancing functional recovery in preclinical rodent models. These findings pave the way for further research and potential clinical translation.
{"title":"Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles in ischemic stroke: A meta-analysis of preclinical studies","authors":"Xiaoming Zhang , Yibing Guo , Kun Fang , Xiangqian Huang , Duo Lan , Mengqi Wang , Lina Jia , Xunming Ji , Ran Meng , Da Zhou","doi":"10.1016/j.brainresbull.2025.111219","DOIUrl":"10.1016/j.brainresbull.2025.111219","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke (IS) remains a significant global health burden, necessitating the development of novel therapeutic strategies. This study aims to systematically evaluate the therapeutic effects of mesenchymal stem cell-derived exosomes (MSC-Exos) on IS outcomes in rodent models.</div></div><div><h3>Methods</h3><div>A comprehensive literature search was conducted across multiple databases to identify studies investigating the effects of MSC-Exos on rodent models of IS. Following rigorous inclusion and exclusion criteria, 73 high-quality studies were selected for meta-analysis. Primary outcomes included reductions in infarct volume/ratio and improvements in functional recovery scores. Data extraction and analysis were performed using RevMan 5.3 software.</div></div><div><h3>Results</h3><div>Pooled data indicated that MSC-Exos administration significantly reduced infarct size and improved functional recovery scores in rodent models of IS. Treatment within 24 hours and beyond 24 hours of stroke induction both demonstrated substantial reductions in infarct volume/ratio compared to controls. Furthermore, MSC-Exos-treated groups exhibited marked improvements in functional recovery, as assessed by various neurobehavioral tests. The meta-analysis showed no significant publication bias, and heterogeneity levels were acceptable.</div></div><div><h3>Conclusions</h3><div>MSC-Exos reveal significant therapeutic potential for IS, with evidence supporting their efficacy in reducing infarct size and enhancing functional recovery in preclinical rodent models. These findings pave the way for further research and potential clinical translation.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111219"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.brainresbull.2025.111209
Sang Seok Yeo , Seo Yoon Park , In Hee Cho
Introduction
The thalamus regulates various sensory information to each related brain area. The vestibular nucleus transmits information of motor control to the thalamus regulating coordination function. The vestibulothalamic tract (VTT) is a neural pathway between the vestibular nucleus and thalamus that processes vestibular information for postural balance and spatial perception. Therefore, this study analyzed ipsilateral VTT to compare the neural pathway and the differences in vestibular and balance functions according to aging.
Methods
Eleven elderly and 12 young healthy adults were recruited. This study measured subjective visual vertical (SVV) for vestibular function and body sway during one-leg standing. The ipsilateral VTT were reconstructed to investigate changes of neural pathway between two groups using diffusion tensor imaging.
Results
Track volume of left and right VTTs was significantly more in the young healthy adults. In eyes-open (EO) condition during one-leg standing, the body sway demonstrated significant differences between two groups. In the eyes-closed (EC) condition, the degree of hip sway was decreased in the young healthy adults. In the EO condition, the body sway except for antero-posterior direction was significantly correlated with VTT. Meanwhile, in the EC condition, hip sway and all values of body sway were negatively correlated with VTT. In addition, the VTT revealed a negative correlation with SVV.
Conclusions
The tract volume of VTT and static balance decreased according to aging. The changes of VTT also affected verticality perception and static balance. Therefore, the study could be helpful in providing the data for patients with thalamus or vestibular injury.
{"title":"Age-related changes in the vestibulothalamic pathway: Association with balance ability and subjective visual vertical of vestibular function","authors":"Sang Seok Yeo , Seo Yoon Park , In Hee Cho","doi":"10.1016/j.brainresbull.2025.111209","DOIUrl":"10.1016/j.brainresbull.2025.111209","url":null,"abstract":"<div><h3>Introduction</h3><div>The thalamus regulates various sensory information to each related brain area. The vestibular nucleus transmits information of motor control to the thalamus regulating coordination function. The vestibulothalamic tract (VTT) is a neural pathway between the vestibular nucleus and thalamus that processes vestibular information for postural balance and spatial perception. Therefore, this study analyzed ipsilateral VTT to compare the neural pathway and the differences in vestibular and balance functions according to aging.</div></div><div><h3>Methods</h3><div>Eleven elderly and 12 young healthy adults were recruited. This study measured subjective visual vertical (SVV) for vestibular function and body sway during one-leg standing. The ipsilateral VTT were reconstructed to investigate changes of neural pathway between two groups using diffusion tensor imaging.</div></div><div><h3>Results</h3><div>Track volume of left and right VTTs was significantly more in the young healthy adults. In eyes-open (EO) condition during one-leg standing, the body sway demonstrated significant differences between two groups. In the eyes-closed (EC) condition, the degree of hip sway was decreased in the young healthy adults. In the EO condition, the body sway except for antero-posterior direction was significantly correlated with VTT. Meanwhile, in the EC condition, hip sway and all values of body sway were negatively correlated with VTT. In addition, the VTT revealed a negative correlation with SVV.</div></div><div><h3>Conclusions</h3><div>The tract volume of VTT and static balance decreased according to aging. The changes of VTT also affected verticality perception and static balance. Therefore, the study could be helpful in providing the data for patients with thalamus or vestibular injury.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111209"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.brainresbull.2025.111223
Jia-Cheng Han , Chi Zhang , Yan-Dong Cai , Yu-Ting Li , Yu-Xuan Shang , Zhu-Hong Chen , Guan Yang , Jia-Jie Song , Dan Su , Ke Bai , Jing-Ting Sun , Yu Liu , Na Liu , Ya Duan , Wen Wang
Introduction
Cognitive fatigue is mainly caused by enduring mental stress or monotonous work, impairing cognitive and physical performance. Natural scene exposure is a promising intervention for relieving cognitive fatigue, but the efficacy of virtual reality (VR) simulated natural scene exposure is unclear. We aimed to investigate the effect of VR natural scene on cognitive fatigue and further explored its underlying neurophysiological alterations with electroencephalogram (EEG) microstates analysis.
Methods
Ten participants performed a 20-minute 1-back task before and after VR intervention while EEG was recorded (pre-task, post-task). Performance was measured with mean accuracy rate (MAR) and mean reaction time (MRT) of the continuous 1-back task. VR simulation of the Canal Town scene was utilized to alleviate cognitive fatigue caused by 1-back tasks. Four resting-state phases were identified: beginning, pre, post, and end phases.
Results
Post-task had a higher MAR and a lower MRT than pre-task. For pre-task, MAR was negatively correlated with trials, while MRT was positively correlated with trials. Four EEG microstates classes (A-D) were identified, and their temporal parameters (mean duration, time coverage and occurrence) and transition probabilities were calculated. After intervention, mean duration and time coverage of class B decreased, all parameters of class C increased, while all parameters of class D decreased. Transition probabilities between classes B and D decreased but increased between classes A and C.
Conclusion
VR simulation of Canal Town scene is a potentially effective method to alleviate cognitive fatigue. Microstate is an electrophysiological trait characteristic of cognitive fatigue and might be used to indicate the effect of VR intervention.
{"title":"Neuroimaging features for cognitive fatigue and its recovery with VR intervention: An EEG microstates analysis","authors":"Jia-Cheng Han , Chi Zhang , Yan-Dong Cai , Yu-Ting Li , Yu-Xuan Shang , Zhu-Hong Chen , Guan Yang , Jia-Jie Song , Dan Su , Ke Bai , Jing-Ting Sun , Yu Liu , Na Liu , Ya Duan , Wen Wang","doi":"10.1016/j.brainresbull.2025.111223","DOIUrl":"10.1016/j.brainresbull.2025.111223","url":null,"abstract":"<div><h3>Introduction</h3><div>Cognitive fatigue is mainly caused by enduring mental stress or monotonous work, impairing cognitive and physical performance. Natural scene exposure is a promising intervention for relieving cognitive fatigue, but the efficacy of virtual reality (VR) simulated natural scene exposure is unclear. We aimed to investigate the effect of VR natural scene on cognitive fatigue and further explored its underlying neurophysiological alterations with electroencephalogram (EEG) microstates analysis.</div></div><div><h3>Methods</h3><div>Ten participants performed a 20-minute 1-back task before and after VR intervention while EEG was recorded (pre-task, post-task). Performance was measured with mean accuracy rate (MAR) and mean reaction time (MRT) of the continuous 1-back task. VR simulation of the Canal Town scene was utilized to alleviate cognitive fatigue caused by 1-back tasks. Four resting-state phases were identified: beginning, pre, post, and end phases.</div></div><div><h3>Results</h3><div>Post-task had a higher MAR and a lower MRT than pre-task. For pre-task, MAR was negatively correlated with trials, while MRT was positively correlated with trials. Four EEG microstates classes (A-D) were identified, and their temporal parameters (mean duration, time coverage and occurrence) and transition probabilities were calculated. After intervention, mean duration and time coverage of class B decreased, all parameters of class C increased, while all parameters of class D decreased. Transition probabilities between classes B and D decreased but increased between classes A and C.</div></div><div><h3>Conclusion</h3><div>VR simulation of Canal Town scene is a potentially effective method to alleviate cognitive fatigue. Microstate is an electrophysiological trait characteristic of cognitive fatigue and might be used to indicate the effect of VR intervention.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111223"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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